Soyeon Ahn

Low-Dose Abdominal CT for Evaluating Suspected Appendicitis

BACKGROUND Computed tomography (CT) has become the predominant test for diagnosing acute appendicitis in adults. In children and young adults, exposure to CT radiation is of particular concern. We evaluated the rate of negative (unnecessary) appendectomy after low-dose versus standard-dose abdominal CT in young adults with suspected appendicitis. METHODS In this single-institution, single-blind, noninferiority trial, we randomly assigned 891 patients with suspected appendicitis to either low-dose CT (444 patients) or standard-dose CT (447 patients). The median radiation dose in terms of dose-length product was 116 mGy·cm in the low-dose group and 521 mGy·cm in the standard-dose group. The primary end point was the percentage of negative appendectomies among all nonincidental appendectomies, with a noninferiority margin of 5.5 percentage points. Secondary end points included the appendiceal perforation rate and the proportion of patients with suspected appendicitis who required additional imaging. RESULTS The negative appendectomy rate was 3.5% (6 of 172 patients) in the low-dose CT group and 3.2% (6 of 186 patients) in the standard-dose CT group (difference, 0.3 percentage points; 95% confidence interval, -3.8 to 4.6). The two groups did not differ significantly in terms of the appendiceal perforation rate (26.5% with low-dose CT and 23.3% with standard-dose CT, P=0.46) or the proportion of patients who needed additional imaging tests (3.2% and 1.6%, respectively; P=0.09). CONCLUSIONS Low-dose CT was noninferior to standard-dose CT with respect to negative appendectomy rates in young adults with suspected appendicitis. (Funded by GE Healthcare Medical Diagnostics and others; ClinicalTrials.gov number, NCT00913380.).

Laparoscopic versus open liver resection for hepatocellular carcinoma: Case-matched study with propensity score matching

BACKGROUND & AIMS Laparoscopic liver resection has gained wide acceptance and is established as a safe alternative to open liver resection. Until now, there is no prospective randomized comparative study between laparoscopic and open liver resection. Previous comparative studies reported minor resections for peripheral tumors, and enrolled small numbers of patients. Moreover, few reported the long term outcomes. The aim of this study is to compare perioperative and long term outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma between two matched groups. METHODS 389 patients underwent liver resection for hepatocellular carcinoma during the period between 2004 and 2013. To overcome selection bias, we performed 1:1 match using propensity score matching between laparoscopic and open liver resection. RESULTS After propensity score matching, 88 patients were included in each group. Laparoscopic group had shorter hospital stay (8 vs. 10 days, p⩽0.001), and lower postoperative morbidity (12.5% vs. 20.4%, p=0.042). The 1-, 3- and 5-year overall survivals were 91.6%, 87.5%, and 76.4%, for laparoscopic group, and were 93.1%, 87.8%, and 73.2%, for open group (p=0.944). The 1-, 3- and 5-year disease free survivals were 69.7%, 52%, and 44.2%, for laparoscopic group, and 74.7%, 49.5%, 41.2%, for open group (p=0.944). CONCLUSIONS Our study showed comparative perioperative and long term outcomes between both groups, providing evidence regarding the safety and efficacy of laparoscopic liver resection for hepatocellular carcinoma.

How to Demonstrate Similarity by Using Noninferiority and Equivalence Statistical Testing in Radiology Research

Demonstrating similarity between compared groups--that is, equivalence or noninferiority of the outcome of one group to the outcome of another group--requires a different analytic approach than determining the difference between groups--that is, superiority of one group over another. Neither a statistically significant difference between groups (P < .05) nor a lack of significant difference (P ≥ .05) from conventional statistical tests provides answers about equivalence/noninferiority. Statistical testing of equivalence/noninferiority generally uses a confidence interval, where equivalence/noninferiority is claimed when the confidence interval of the difference in outcome between compared groups is within a predetermined equivalence/noninferiority margin that represents a clinically or scientifically acceptable range of differences and is typically described by Δ. The equivalence/noninferiority margin should be justified both clinically and statistically, considering the loss in the main outcome and the compensatory gain, and be chosen conservatively to avoid making a false claim of equivalence/noninferiority for an inferior outcome. Sample size estimation needs to be specified for equivalence/noninferiority design, considering Δ in addition to other general factors. The need for equivalence/noninferiority research studies is expected to increase in radiology, and a good understanding of the fundamental principles of the methodology will be helpful for conducting as well as for interpreting such studies.

Prevalence and Outcomes of Frailty in Korean Elderly Population: Comparisons of a Multidimensional Frailty Index with Two Phenotype Models

Background Frailty is related to adverse outcomes in the elderly. However, current status and clinical significance of frailty have not been evaluated for the Korean elderly population. We aimed to investigate the usefulness of established frailty criteria for community-dwelling Korean elderly. We also tried to develop and validate a new frailty index based on a multidimensional model. Methods We studied 693 participants of the Korean Longitudinal Study on Health and Aging (KLoSHA). We developed a new frailty index (KLoSHA Frailty Index, KFI) and compared predictability of it with the established frailty indexes from the Cardiovascular Health Study (CHS) and Study of Osteoporotic Fracture (SOF). Mortality, hospitalization, and functional decline were evaluated. Results The prevalence of frailty was 9.2% (SOF index), 13.2% (CHS index), and 15.6% (KFI). The criteria from CHS and KFI correlated with each other, but SOF did not correlate with KFI. During the follow-up period (5.6±0.9 years), 97 participants (14.0%) died. Frailty defined by KFI predicted mortality better than CHS index (c-index: 0.713 and 0.596, respectively; p<0.001, better for KFI). In contrast, frailty by SOF index was not related to mortality. The KFI showed better predictability for following functional decline than CHS index (area under the receiver-operating characteristic curve was 0.937 for KFI and 0.704 for CHS index, p = 0.001). However, the SOF index could not predict subsequent functional decline. Frailty by the KFI (OR = 2.13, 95% CI 1.04–4.35) and CHS index (OR = 2.24, 95% CI 1.05–4.76) were associated with hospitalization. In contrast, frailty by the SOF index was not correlated with hospitalization (OR = 1.43, 95% CI 0.68–3.01). Conclusion Prevalence of frailty was higher in Korea compared to previous studies in other countries. A novel frailty index (KFI), which includes domains of comprehensive geriatric assessment, is a valid criterion for the evaluation and prediction of frailty in the Korean elderly population.

Pitfalls and Important Issues in Testing Reliability Using Intraclass Correlation Coefficients in Orthopaedic Research

Background Intra-class correlation coefficients (ICCs) provide a statistical means of testing the reliability. However, their interpretation is not well documented in the orthopedic field. The purpose of this study was to investigate the use of ICCs in the orthopedic literature and to demonstrate pitfalls regarding their use. Methods First, orthopedic articles that used ICCs were retrieved from the Pubmed database, and journal demography, ICC models and concurrent statistics used were evaluated. Second, reliability test was performed on three common physical examinations in cerebral palsy, namely, the Thomas test, the Staheli test, and popliteal angle measurement. Thirty patients were assessed by three orthopedic surgeons to explore the statistical methods testing reliability. Third, the factors affecting the ICC values were examined by simulating the data sets based on the physical examination data where the ranges, slopes, and interobserver variability were modified. Results Of the 92 orthopedic articles identified, 58 articles (63%) did not clarify the ICC model used, and only 5 articles (5%) described all models, types, and measures. In reliability testing, although the popliteal angle showed a larger mean absolute difference than the Thomas test and the Staheli test, the ICC of popliteal angle was higher, which was believed to be contrary to the context of measurement. In addition, the ICC values were affected by the model, type, and measures used. In simulated data sets, the ICC showed higher values when the range of data sets were larger, the slopes of the data sets were parallel, and the interobserver variability was smaller. Conclusions Care should be taken when interpreting the absolute ICC values, i.e., a higher ICC does not necessarily mean less variability because the ICC values can also be affected by various factors. The authors recommend that researchers clarify ICC models used and ICC values are interpreted in the context of measurement.

Prevalence, risk factors and comorbidities of allergic rhinitis in South Korea: The Fifth Korea National Health and Nutrition Examination Survey.

Background There has been no nationwide epidemiological investigation of allergic rhinitis (AR) that was diagnosed by both questionnaires and laboratory tests in Korea. This study investigated the prevalence, risk factors, and comorbidities of AR in South Korea. Methods The Korean National Health and Nutritional Examination Survey examined a representative sample of the Korean population. A total of 2305 participants underwent immunoradiometric assay for specific IgE antibodies against common indoor allergens. Healthy, atopy only, and AR groups were defined according to the results of allergen test. The weighted prevalence for each group was calculated. Risk factors including food and comorbidities were identified using univariate or multivariate analyses. The patients were also categorized into four subgroups according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) classification and associated comorbidities were analyzed. Results The prevalence of atopy only and AR was 30.0 ± 1.2% and 16.2 ± 1.0%, respectively. The multivariate analysis showed that the prevalence was influenced by sex (p < 0.01) for atopy only and sex (p = 0.09), age (p = 0.02), marital status (p = 0.24), and stress level (p = 0 for AR. Compared with the healthy group, asthma (odds ratio [OR] = 4.77), nasal polyp (NP; OR = 3.44), chronic rhinosinusitis (OR = 13.93), and olfactory dysfunction (OR = 4.88) were more prevalent in the AR group. Based on the ARIA guideline, intermittent mild rhinitis was most common (58.1%). Asthma was correlated to severity and atopic dermatitis and NPs was associated with persistency. Daily intake of less mackerel and more carrots, bread, and bean curd were associated with the increased risk of AR. Conclusion Prevalence, risk factors, and comorbidities of AR were evaluated in the general Korean population, which will contribute to prevention and treatment of AR and its comorbidities in Koreans.

Seroprevalence of anti-hepatitis E virus (HEV) in a Korean population: comparison of two commercial anti-HEV assays

BackgroundHepatitis E virus (HEV) has emerged as an important cause of epidemic and sporadic acute viral hepatitis worldwide. This study investigated the seroprevalence of anti-HEV in a Korean population and compared the performance of two commercially available anti-HEV assays.MethodsA total 147 health-check examinees were randomly sampled as matched to the age- and sex- adjusted standard population based on the Korean National Census of 2007. Serum immunoglobulin G anti-HEV was determined by using the Genelabs assay (Genelabs, Singapore) and the Wantai assay (Wantai, Beijing, China).ResultsThe overall anti-HEV seroprevalence was 23.1% (95% CI, 16.1-30.1%) using the Wantai assay and 14.3% (95% CI, 8.3-20.3%) using the Genelabs assay. Only 12 samples (8.1%) were positive for anti-HEV as measured by both assays; agreement between the two assays was poor (kappa value of 0.315). The anti-HEV seroprevalence increased with age from 2% and 3% in the people younger than 20-years-of-age to 34.6% and 42.3% in those over 59-years-of-age by the Genelabs and Wantai assay, respectively.ConclusionsThe HEV seroprevalence in Korean population is about 20% overall, with seroprevalence increasing in this population with increasing age. There was poor concordance in the results of the Genelabs and Wantai assays, which warrants further study concerning a reliable diagnostic test for the diagnosis of hepatitis E.

Prevalence of Subjective Olfactory Dysfunction and Its Risk Factors: Korean National Health and Nutrition Examination Survey

Background Population-based studies for olfactory dysfunction are lacking. The aim of this study is to evaluate the prevalence of subjective olfactory dysfunction and its risk factors in the Korean general population. Methods The data were obtained from the 2009 Korea National Health and Nutrition Examination Survey (KNHANES), which was a cross-sectional survey of non-institutionalized population all around the country (n = 10,533). All interviewees underwent medical interviews, physical examinations, endoscopic examination and blood/urine tests. Whether sense of smell has been normal or abnormal during the last 3 months was asked. Complete olfaction data were obtained from 7,306 participants and the participants were divided into normosmic and hyposmic group. Multivariate logistic regression analyses were performed to identify its risk factors. Results The weighted prevalence of subjective olfactory dysfunction was 4.5%. Its increased prevalence was significantly associated with the increasing age for both men and women. In the multivariate analyses, low income (adjusted odds ratio [OR] = 1.43, 95% Confidence Interval [CI] = 1.01–2.03), habitual exposure to air pollutants (adjusted OR = 2.18, CI = 1.33–3.55), a history of hepatitis B (adjusted OR = 3.10, CI = 1.25–7.68), rhinitis (adjusted OR = 1.78, CI = 1.26–2.51) and chronic sinusitis (adjusted OR = 14.55, CI = 10.06–21.05) were risk factors of olfactory dysfunction. Conclusion Our population-based study showed that olfactory dysfunction was quite prevalent and several risk factors were associated with impaired sense of smell. Given its prevalence, further researches for its prevention and management are required.

Clinical features and outcome of cryptogenic hepatocellular carcinoma compared to those of viral and alcoholic hepatocellular carcinoma

BackgroundCryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALC-HCC) in Korea.MethodsThe clinical features, treatment modalities, and survival data for 480 patients with HCC consecutively enrolled from January 2003 to June 2012 were analyzed. Computed tomography images were used to measure the visceral fat area (VFA) and liver-spleen density ratio.ResultsCryptogenic HCC accounted for 6.8% of all HCC cases, whereas HBV-HCC, HCV-HCC, and ALC-HCC accounted for 62.7%, 13.5%, and 10.7% of HCC cases, respectively. The cryptogenic HCC group was characterized by older age, a low proportion of male patients, a high proportion of patients with metabolic syndrome or single nodular presentation, and a low proportion of patients with portal vein invasion compared to the viral-HCC and ALC-HCC groups. However, Child Pugh classes, tumor stages, and overall survival rates of cryptogenic HCC patients were similar to those of patients with HCC of other etiologies. VFA in cryptogenic HCC patients was significantly higher than that in viral-HCC patients, but similar to that in ALC-HCC patients. The liver-spleen density ratio did not vary according to HCC etiology.ConclusionsCryptogenic HCC accounts for approximately 7% of HCC cases in Korea, associated with an older age at diagnosis, more frequent occurrence of metabolic syndrome, and less aggressive tumor characteristics, but similar survival compared to viral-HCC or ALC-HCC. Based on VFA and the liver-to-spleen density ratio, cryptogenic HCC may be burnt-out NAFLD in which visceral fat remains but liver fat is depleted.

Systemic Analysis of Heat Shock Response Induced by Heat Shock and a Proteasome Inhibitor MG132

The molecular basis of heat shock response (HSR), a cellular defense mechanism against various stresses, is not well understood. In this, the first comprehensive analysis of gene expression changes in response to heat shock and MG132 (a proteasome inhibitor), both of which are known to induce heat shock proteins (Hsps), we compared the responses of normal mouse fibrosarcoma cell line, RIF- 1, and its thermotolerant variant cell line, TR-RIF-1 (TR), to the two stresses. The cellular responses we examined included Hsp expressions, cell viability, total protein synthesis patterns, and accumulation of poly-ubiquitinated proteins. We also compared the mRNA expression profiles and kinetics, in the two cell lines exposed to the two stresses, using microarray analysis. In contrast to RIF-1 cells, TR cells resist heat shock caused changes in cell viability and whole-cell protein synthesis. The patterns of total cellular protein synthesis and accumulation of poly-ubiquitinated proteins in the two cell lines were distinct, depending on the stress and the cell line. Microarray analysis revealed that the gene expression pattern of TR cells was faster and more transient than that of RIF-1 cells, in response to heat shock, while both RIF-1 and TR cells showed similar kinetics of mRNA expression in response to MG132. We also found that 2,208 genes were up-regulated more than 2 fold and could sort them into three groups: 1) genes regulated by both heat shock and MG132, (e.g. chaperones); 2) those regulated only by heat shock (e.g. DNA binding proteins including histones); and 3) those regulated only by MG132 (e.g. innate immunity and defense related molecules). This study shows that heat shock and MG132 share some aspects of HSR signaling pathway, at the same time, inducing distinct stress response signaling pathways, triggered by distinct abnormal proteins.