Beeswax Alcohol Prevents Low-Density Lipoprotein Oxidation and Demonstrates Antioxidant Activities in Zebrafish Embryos and Human Subjects: A Clinical Study.

Oxidative stress is one of the primary instigators of the onset of various human ailments, including cancers, cardiovascular diseases, and dementia. Particularly, oxidative stress severely affects low-density lipid & protein (LDL) oxidation, leading to several detrimental health effects. Therefore, in this study, the effect of beeswax alcohol (BWA) was evaluated in the prevention of LDL oxidation, enhancement of paraoxonase 1 (PON-1) activity of high-density lipid & protein (HDL), and zebrafish embryo survivability. Furthermore, the implication of BWA consumption on the oxidative plasma variables was assessed by a preliminary clinical study on middle-aged and older human subjects (n = 50). Results support BWA augmentation of PON-1 activity in a dose-dependent manner (10-30 µM), which was significantly better than the effect exerted by coenzyme Q10 (CoQ10). Moreover, BWA significantly curtails LDL/apo-B oxidation evoked by CuSO4 (final 0.5 µM) and a causes a marked reduction in lipid peroxidation in LDL. The transmission electron microscopy (TEM) analysis revealed a healing effect of BWA towards the restoration of LDL morphology and size impaired by the exposure of Cu2+ ions (final 0.5 µM). Additionally, BWA counters the toxicity induced by carboxymethyllysine (CML, 500 ng) and rescues zebrafish embryos from development deformities and apoptotic cell death. A completely randomized, double-blinded, placebo-controlled preliminary clinical study on middle- and older-aged human subjects (n = 50) showed that 12 weeks of BWA (100 mg/day) supplementation efficiently diminished serum malondialdehyde (MDA) and total hydroperoxides and enhanced total antioxidant status by 25%, 27%, and 22%, respectively, compared to the placebo-control and baseline values. Furthermore, the consumption of BWA did not exhibit any noteworthy changes in physical variables, lipid profile, glucose levels, and biomarkers pertinent to kidney and liver function, thus confirming the safety of BWA for consumption. Conclusively, in vitro, BWA prevents LDL oxidation, enhances PON-1 activity in HDL, and positively influences oxidative variables in human subjects.

Beneficial Effect of Cuban Policosanol on Blood Pressure and Serum Lipoproteins Accompanied with Lowered Glycated Hemoglobin and Enhanced High-Density Lipoprotein Functionalities in a Randomized, Placebo-Controlled, and Double-Blinded Trial with Healthy Japanese.

This study evaluated the efficacy and safety of 20 mg of Cuban policosanol in blood pressure (BP) and lipid/lipoprotein parameters of healthy Japanese subjects via a placebo-controlled, randomized, and double-blinded human trial. After 12 weeks of consumption, the policosanol group showed significantly lower BP, glycated hemoglobin (HbA1c), and blood urea nitrogen (BUN) levels. The policosanol group also showed lower aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GTP) levels at week 12 than those at week 0: A decrease of up to 9% (p < 0.05), 17% (p < 0.05), and 15% (p < 0.05) was observed, respectively. The policosanol group showed significantly higher HDL-C level and HDL-C/TC (%), approximately 9.5% (p < 0.001) and 7.2% (p = 0.003), respectively, than the placebo group and a difference in the point of time and group interaction (p < 0.001). In lipoprotein analysis, the policosanol group showed a decrease in oxidation and glycation extent in VLDL and LDL with an improvement of particle shape and morphology after 12 weeks. HDL from the policosanol group showed in vitro stronger antioxidant and in vivo anti-inflammatory abilities. In conclusion, 12 weeks of Cuban policosanolconsumption in Japanese subjects showed significant improvement in blood pressure, lipid profiles, hepatic functions, and HbA1c with enhancement of HDL functionalities.

Comparison of Policosanols via Incorporation into Reconstituted High-Density Lipoproteins: Cuban Policosanol (Raydel®) Exerts the Highest Antioxidant, Anti-Glycation, and Anti-Inflammatory Activity.

Reconstituted high-density lipoproteins (rHDL) containing each policosanol from Cuba (Raydel®), China (Shaanxi Pioneer), and the United States (Lesstanol®) were synthesized to compare the physiological properties of policosanol depending on sources and origin countries. After synthesis with apolipoproteinA-I (apoA-I) into rHDL, all policosanols bound well with phospholipid and apoA-I to form discoidal rHDL. An rHDL containing Cuban policosanol (rHDL-1) showed the largest rHDL particle size of around 83 ± 3 nm, while rHDL containing Chinese policosanol (rHDL-2) or American policosanol (rHDL-3) showed smaller particles around 63 ± 3 nm and 60 ± 2 nm in diameter, respectively. The rHDL-1 showed the strongest anti-glycation activity to protect the apoA-I degradation of HDL from fructose-mediated glycation: approximately 2.7-times higher ability to suppress glycation and 1.4-times higher protection ability of apoA-I than that of rHDL-2 and rHDL-3. The rHDL-1 showed the highest antioxidant ability to inhibit cupric ion-mediated LDL oxidation in electromobility and the quantification of oxidized species. A microinjection of each rHDL into a zebrafish embryo in the presence of carboxymethyllysine (CML) showed that rHDL-1 displayed the strongest anti-oxidant activity with the highest embryo survivability, whereas rHDL-2 and rHDL-3 showed much weaker protection ability, similar to rHDL alone (rHDL-0). An intraperitoneal injection of CML (250 µg) into adult zebrafish caused acute death and hyperinflammation with an elevation of infiltration of neutrophils and IL-6 production in the liver. On the other hand, a co-injection of rHDL-1 resulted in the highest survivability and the strongest anti-inflammatory ability to suppress IL-6 production with an improvement of the blood lipid profile, such as elevation of HDL-C and lowering of the total cholesterol, LDL-cholesterol, and triglyceride. In conclusion, Cuban policosanol exhibited the most desirable properties for the in vitro synthesis of rHDL with the stabilization of apoA-I, the largest particle size, anti-glycation against fructation, and antioxidant activities to prevent LDL oxidation. Cuban policosanol in rHDL also exhibited the strongest in vivo antioxidant and anti-inflammatory activities with the highest survivability in zebrafish embryos and adults via the prevention of hyperinflammation in the presence of CML.

Reliability of fast magnetic resonance imaging for acute ischemic stroke patients using a 1.5-T scanner.

OBJECTIVES: To determine whether fast scanned MRI using a 1.5-T scanner is a reliable method for the detection and characterization of acute ischemic stroke in comparison with conventional MRI. METHODS: From May 2015 to June 2016, 862 patients (FLAIR, n = 482; GRE, n = 380; MRA, n = 190) were prospectively enrolled in the study, with informed consent and under institutional review board approval. The patients underwent both fast (EPI-FLAIR, ETL-FLAIR, TR-FLAIR, EPI-GRE, parallel-GRE, fast CE-MRA) and conventional MRI (FLAIR, GRE, time-of-flight MRA, fast CE-MRA). Two neuroradiologists independently assessed agreements in acute and chronic ischemic hyperintensity, hyperintense vessels (FLAIR), microbleeds, susceptibility vessel signs, hemorrhagic transformation (GRE), stenosis (MRA), and image quality (all MRI), between fast and conventional MRI. Agreements between fast and conventional MRI were evaluated by generalized estimating equations. Z-scores were used for comparisons of the percentage agreement among fast FLAIR sequences and fast GRE sequences and between conventional and fast MRA. RESULTS: Agreements of more than 80% were achieved between fast and conventional MRI (ETL-FLAIR, 96%; TR-FLAIR, 97%; EPI-GRE, 96%; parallel-GRE, 98%; fast CE-MRA, 86%). ETL- and TR-FLAIR were significantly superior to EPI-FLAIR in the detection of acute ischemic hyperintensity and hyperintense vessels, while parallel-GRE was significantly superior to EPI-GRE in the detection of susceptibility vessel sign (p value < 0.05 for all). There were no significant differences in the other scores and image qualities (p value > 0.05). CONCLUSIONS: Fast MRI at 1.5 T is a reliable method for the detection and characterization of acute ischemic stroke in comparison with conventional MRI. KEY POINTS: • Fast MRI at 1.5 T may achieve a high intermethod reliability in the detection and characterization of acute ischemic stroke with a reduction in scan time in comparison with conventional MRI.

Coronary CT angiography characteristics of OCT-defined thin-cap fibroatheroma: a section-to-section comparison study.

OBJECTIVES: To evaluate whether plaque characteristics as assessed by coronary computed tomography angiography (CCTA) were associated with the presence of a thin-cap fibroatheroma (TCFA)-a precursor of plaque rupture-defined by optical coherence tomography (OCT) in a section-to-section-level comparison. METHODS: From 28 symptomatic patients, 31 coronary lesions were evaluated on 727 cross-sections co-registered by both CCTA and OCT. CCTA plaque characteristics included low attenuation plaque (LAP, <30 HU), napkin ring sign (NRS), positive remodelling (PR, remodelling index ≥1.10), and spotty calcification and plaque area and plaque burden. By OCT, presence of TCFA, lumen area and arc of lipid were determined. RESULTS: OCT revealed a TCFA in 69 (9.4%) sections from 19 (61.2 %) lesions. In per-section analysis, OCT-TCFA showed higher frequency of CCTA-detected LAP (58.0% vs. 18.5%), NRS (31.9% vs. 8.8%) and PR (68.1% vs. 48.0%) and greater plaque burden (70.6% vs. 61.9%) as compared to sections without OCT-TCFA (all p < 0.05). In multivariable analysis, LAP (odds ratio [OR] 4.05, p < 0.001) and NRS (OR 2.47, p = 0.005) were associated with OCT-TCFA. CCTA-measured lumen area correlated well with OCT-measured lumen area (R = 0.859, limits of agreement -0.5 ± 3.7 mm2). CONCLUSIONS: LAP and NRS in CCTA were associated with the presence of OCT-defined TCFA in a section-to-section comparison. KEY POINTS: • CT-defined LAP and NRS were associated with OCT-defined TCFA • OCT-TCFA showed higher frequency of LAP, NRS, PR and greater plaque burden • Non-calcified plaque area was correlated with OCT-measured lipid arc.

Usefulness of argon plasma coagulation ablation subsequent to endoscopic snare papillectomy for ampullary adenoma.

BACKGROUND AND AIM: Endoscopic snare papillectomy (ESP) is an effective treatment for ampullary adenoma. Argon plasma coagulation (APC) is widely used as an additional method to control bleeding or ablate the residual tumor. However, the efficacy of this procedure has not yet been fully evaluated. This study aimed to evaluate the usefulness of APC as an additional method to ESP. METHODS: Patients who underwent ESP for ampullary adenoma between September 2005 and September 2015 were retrospectively reviewed. Using propensity score matching, we compared short- and long-term outcomes between the ESP-with-additional-APC group (ESP + APC group) and the ESP-only group. Primary outcome was early post-ESP adverse events (AE), and secondary outcomes were late AE and recurrence. RESULTS: Among 109 patients, additional APC was carried out in 59 (54.1%) patients. After matching, 41 patients were included in both groups, respectively. Bleeding rate was significantly lower in the ESP + APC group than in the ESP-only group (7.3% vs 31.7%, odds ratio = 0.180, P < 0.01). However, there were no significant differences in other procedure-related early AE such as pancreatitis (12.2% vs 19.5%, P = 0.365), cholangitis (2.4% vs 9.8%, P = 0.198), and perforation (2.4% vs 2.4%, P = 1.000) between the ESP + APC group and the ESP-only group. During the follow-up period (mean 904 ± 868 days), papillary stricture (9.8% vs 4.9%, P = 0.405) and recurrence rates (24.4% vs 24.4%, P = 0.797) were not significantly different between the ESP + APC group and the ESP-only group. CONCLUSION: Additional APC during ESP may have a beneficial effect by decreasing bleeding rate without harmful effects.

Myocardial segmentation based on coronary anatomy using coronary computed tomography angiography: Development and validation in a pig model.

OBJECTIVES: To validate a method for performing myocardial segmentation based on coronary anatomy using coronary CT angiography (CCTA). METHODS: Coronary artery-based myocardial segmentation (CAMS) was developed for use with CCTA. To validate and compare this method with the conventional American Heart Association (AHA) classification, a single coronary occlusion model was prepared and validated using six pigs. The unstained occluded coronary territories of the specimens and corresponding arterial territories from CAMS and AHA segmentations were compared using slice-by-slice matching and 100 virtual myocardial columns. RESULTS: CAMS more precisely predicted ischaemic area than the AHA method, as indicated by 95% versus 76% (p < 0.001) of the percentage of matched columns (defined as percentage of matched columns of segmentation method divided by number of unstained columns in the specimen). According to the subgroup analyses, CAMS demonstrated a higher percentage of matched columns than the AHA method in the left anterior descending artery (100% vs. 77%; p < 0.001) and mid- (99% vs. 83%; p = 0.046) and apical-level territories of the left ventricle (90% vs. 52%; p = 0.011). CONCLUSIONS: CAMS is a feasible method for identifying the corresponding myocardial territories of the coronary arteries using CCTA. KEY POINTS: • CAMS is a feasible method for identifying corresponding coronary territory using CTA • CAMS is more accurate in predicting coronary territory than the AHA method • The AHA method may underestimate the ischaemic territory of LAD stenosis.

Subtraction Images of Gadoxetic Acid-Enhanced MRI: Effect on the Diagnostic Performance for Focal Hepatic Lesions in Patients at Risk for Hepatocellular Carcinoma.

OBJECTIVE: The purpose of this study is to evaluate the effect of subtraction images of gadoxetic acid-enhanced MRI on the image interpretation of focal hepatic lesions in patients at risk for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We retrospectively analyzed 255 malignant nodules from 233 patients with chronic hepatitis or liver cirrhosis (187 men and 46 women; mean age, 55.2 years) who underwent preoperative gadoxetic acid-enhanced MRI and surgical resection. We compared the detection rate of arterial hypervascularity on visual assessment with that of subtraction images. Subgroup analysis was performed according to the pathologic profile of the lesion (HCC vs non-HCC), the lesion size (≤ 3 vs > 3 cm), and the MRI technique (1.5 vs 3 T). We assessed the effect of subtraction images in diagnosing HCC according to the American Association for the Study of Liver Diseases guidelines compared with that of visual assessment. RESULTS: After excluding six patients whose images were not of nondiagnostic quality, 249 nodules (215 HCCs, 27 cholangiocarcinomas, and seven combined HCC and cholangiocarcinomas) from 227 patients were analyzed. Subtraction images more sensitively detected the arterial hypervascularity of all of the hepatic lesions than did visual assessment (sensitivity, 89.2% vs 72.4%; p < 0.001). In all of the subgroup analyses, the same tendency was observed (p = 0.001-0.145). Compared with visual assessment only, arterial hypervascularity determined by both subtraction images and the visual enhancement patterns increased sensitivity from 76.5% to 87.5% (p < 0.001) in diagnosing HCCs, with a minimal decrease in specificity from 80.9% to 78.1% (p = 0.332). CONCLUSION: Adding subtraction images with consideration of visual enhancement patterns can enhance the sensitivity in diagnosing HCC by enhancing the detection of arterial hypervascularity.

MR Enterography for the Evaluation of Small-Bowel Inflammation in Crohn Disease by Using Diffusion-weighted Imaging without Intravenous Contrast Material: A Prospective Noninferiority Study.

PURPOSE: To determine whether magnetic resonance (MR) enterography performed with diffusion-weighted imaging (DWI) without intravenous contrast material is noninferior to contrast material-enhanced (CE) MR enterography for the evaluation of small-bowel inflammation in Crohn disease. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for this prospective noninferiority study. Fifty consecutive adults suspected of having Crohn disease underwent clinical assessment, MR enterography, and ileocolonoscopy within 1 week. MR enterography included conventional imaging and DWI (b = 900 sec/mm(2)). In 44 patients with Crohn disease, 171 small-bowel segments that were generally well distended and showed a wide range of findings, from normalcy to severe inflammation (34 men, 10 women; mean age ± standard deviation, 26.9 years ± 6.1), were selected for analysis. Image sets consisting of (a) T2-weighted sequences with DWI and (b) T2-weighted sequences with CE T1-weighted sequences were reviewed by using a crossover design with blinding and randomization. Statistical analyses included noninferiority testing regarding proportional agreement between DWI and CE MR enterography for the identification of bowel inflammation with a noninferiority margin of 80%, correlation between DWI and CE MR enterography scores of bowel inflammation severity, and comparison of accuracy between DWI and CE MR enterography for the diagnosis of terminal ileal inflammation by using endoscopic findings as the reference standard. RESULTS: The agreement between DWI and CE MR enterography for the identification of bowel inflammation was 91.8% (157 of 171 segments; one-sided 95% confidence interval: ≥88.4%). The correlation coefficient between DWI and CE MR enterography scores was 0.937 (P < .001). DWI and CE MR enterography did not differ significantly regarding the sensitivity and specificity for the diagnosis of terminal ileal inflammation (P > .999). DWI and CE MR enterography concurred in the diagnosis of penetrating complications in five of eight segments. CONCLUSION: DWI MR enterography was noninferior to CE MR enterography for the evaluation of inflammation in Crohn disease in generally well-distended small bowel, except for the diagnosis of penetration.

Tumor apparent diffusion coefficient as an imaging biomarker to predict tumor aggressiveness in patients with estrogen-receptor-positive breast cancer.

The purpose of this retrospective study was to evaluate whether tumor apparent diffusion coefficient (ADC) was correlated with pathologic biomarkers such as tumor cellularity, Ki67, tumor-infiltrating lymphocytes (TILs), and peritumoral lymphocytic infiltrate (PLI) in patients with estrogen receptor (ER)-positive breast cancer. The study was approved by the institutional review board and informed consent was waived. From July 2014 to December 2014, we reviewed 140 ER-positive tumors in 138 consecutive patients (range, 28-77 years; mean, 52 years) who underwent preoperative breast MRI and definitive surgery. All patients underwent diffusion-weighted imaging with a 3T scanner. Two radiologists drew the region of interest of the entire tumor and obtained the mean and pixel-based histogram of ADC. On pathology, two pathologists reviewed tumor cellularity, Ki67, TILs, and PLI. Multiple linear regression analysis was used to determine pathologic variables independently associated with ADC. Tumors with high tumor cellularity and high Ki67 had significantly lower ADCs than those with low tumor cellularity and low Ki67 (P < 0.05 for all). Tumors without PLI had significantly higher standard deviation than those with PLI (0.23 ± 0.08 versus 0.18 ± 0.05; P < 0.001). Median ADC was negatively correlated with tumor cellularity (r = -0.441), and Ki67 (r = -0.382). The standard deviation of ADC was also negatively correlated with the degree of PLI (r = -0.319). On multivariate linear regression analysis, tumor cellularity and Ki67 were independently associated with tumor ADC. Tumor ADC would be an MRI biomarker for the prediction of tumor aggressiveness indicators such as Ki67, tumor cellularity, and PLI in ER-positive breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of pregnancy in asthma on health care use and perinatal outcomes.

BACKGROUND: It is generally known that pregnancy in asthmatic patients increases the risk of asthma exacerbations and poor perinatal outcomes. However, the effect of pregnancy in asthmatic patients on health care use is not known well. In addition, its effect on perinatal outcomes is still controversial because of study limitations caused by ethical issues. National Health Insurance claim data are an ideal resource for studying real-world health care use patterns of asthma. OBJECTIVE: We sought to evaluate the effect of pregnancy on asthma in terms of asthma-related health care use and prescription patterns in concert with the effect of asthma exacerbations on adverse pregnancy outcomes. METHODS: Among all asthmatic patients in the Korean National Health Insurance claim database from January 2009 to December 2013, pregnant women who delivered in 2011 with pre-existing asthma were enrolled. Analyses included asthma-related health care use and prescription patterns compared between pregnant asthmatic women and nonpregnant female asthmatic control subjects, as well as within the pregnant subjects from before pregnancy throughout postpartum periods. In addition, the association between asthma exacerbation during pregnancy and adverse pregnancy outcomes was assessed. RESULTS: A total of 3,357 pregnant asthmatic patients were compared with 50,355 nonpregnant asthmatic patients, and 10,311 pregnant patients were included to determine the effect of asthma exacerbations on adverse pregnancy outcome in the study. Pregnant asthmatic patients underwent more asthma-related hospitalizations (1.3% vs 0.8%, P = .005) but had significantly fewer outpatient visits and prescriptions for most asthma medications than nonpregnant asthmatic patients. The proportion of patients ever hospitalized gradually increased throughout pregnancy (first trimester, 0.2%; second trimester, 0.5%; and third trimester, 0.7%; P = .018). The prevalence of asthma exacerbation during pregnancy was 5.3%, and the patients who had acute exacerbation during pregnancy had significantly higher asthma-related health care use in terms of hospitalization, intensive care unit admission, and emergency department and outpatient visits within 1 year before delivery than those who had not. However, asthma exacerbation during pregnancy was not significantly related to adverse perinatal outcomes, except for cesarean section (27.1% vs 18.9%, P < .001). All exacerbations were managed with systemic corticosteroids, and the patients who ever experienced acute exacerbations maintained asthma medications, including inhaled corticosteroid-based inhalers, throughout the pregnancy period. CONCLUSION: Pregnancy profoundly affects asthma-related health care use but to a different degree depending on whether the patient experienced an exacerbation. Asthma exacerbation during pregnancy is not associated with adverse pregnancy outcomes while managed appropriately with systemic corticosteroids. However, further studies are needed to clarify the effect of asthma control on perinatal outcome and delivery method.

Simethicone to prevent colonic bubbles during CT colonography performed with polyethylene glycol lavage and iohexol tagging: a randomized clinical trial.

OBJECTIVE: The purpose of this study was to determine whether the occurrence of numerous colonic bubbles during CT colonography (CTC) performed with polyethylene glycol cleansing and oral iohexol fecal/fluid tagging could be prevented by use of simethicone. SUBJECTS AND METHODS: Adults with suspected colonic neoplasia who had been randomly assigned to control and simethicone intervention groups underwent CTC after cleansing with 4 L of polyethylene glycol, tagging with 50 mL of 350 mg I/mL oral iohexol, and without (control) or with (intervention) oral administration of 200 mg of simethicone. Colonic segments in the control and intervention groups were evaluated for amount of colonic bubbles during CTC. A 6-point grading system was used in which 0 indicated no bubbles and 5 indicated that more than three fourths of the air-distended mucosa was covered with bubbles. The primary endpoint was a per-patient colonic bubble grade, derived as an average of the segmental grades. RESULTS: Eighty adults with suspected colonic neoplasia were randomly assigned to the control (40 patients) and simethicone intervention (40 patients) groups. A total of 659 colonic segments in the control group and 689 segments in the intervention group were evaluated for amount of colonic bubbles during CTC. The per-patient colonic bubble score was significantly lower in the simethicone intervention group than in the control group. The mean score was 0.0±0.1 (SD) versus 1.2±0.8 (p<0.001; 95% CI for the mean difference, -1.4 to -1.0). In the intervention group, 673 (97.7%) segments were grade 0, and 16 (2.3%) were grade 1. In contrast, in the control group, 226 (34.3%) segments were grade 0; 173 (26.3%), grade 1; 175 (26.6%), grade 2; 45 (6.8%), grade 3; 23 (3.5%), grade 4; and 17 (2.6%), grade 5. CONCLUSION: The colonic bubbles associated with fecal/fluid tagging with iohexol can be successfully prevented by adding simethicone to the colonic preparation.

New scoring system for the differentiation of chronic obstructive pulmonary disease and asthma.

BACKGROUND AND OBJECTIVE: It remains difficult to differentiate between chronic obstructive pulmonary disease (COPD) and asthma in clinical practice, especially in a primary care setting. The purpose of this study was to develop a new scoring system for differentiating between COPD and asthma, and to evaluate its effectiveness. METHODS: First, to identify important variables differentiating COPD from asthma, the data of 197 patients with COPD and 138 patients with asthma were assessed retrospectively. Secondly, a scoring system that was based on these variables was then developed, and its performance was internally validated using a bootstrapping-based method. Thirdly, the scoring system was externally validated using prospectively collected data from patients with COPD (n = 104) or asthma (n = 96). RESULTS: The final scoring system was composed of the four variables: age of onset of breathlessness (<40 years, 0 points; 40-60 years, 2 points; >60 years, 4 points), continuous breathlessness (no, 0 points; yes, 1 point), diurnal variation of breathlessness (yes, 0 points; no, 1 point) and emphysematous change in chest X-ray (no, 0 points; yes, 1 point). The patients were classified by their total score into three categories: 0-2 points, probable asthma; 3-4 points, difficult-to-differentiate; 5-7 points, probable COPD. The new scoring system performed well in the external validation dataset (area under the curve, 0.86; 95% confidence interval: 0.813-0.911; P < 0.001). CONCLUSIONS: The new scoring system that was developed in this study may be a useful tool for differentiating between COPD and asthma in primary care.

Relationship between Serum Uric Acid Concentration and Acute Kidney Injury after Coronary Artery Bypass Surgery.

An elevated serum concentration of uric acid may be associated with an increased risk of acute kidney injury (AKI). The aim of this study was to investigate the impact of preoperative uric acid concentration on the risk of AKI after coronary artery bypass surgery (CABG). Perioperative data were evaluated from patients who underwent CABG. AKI was defined by the AKI Network criteria based on serum creatinine changes within the first 48 hr after CABG. Multivariate logistic regression was utilized to evaluate the association between preoperative uric acid and postoperative AKI. We evaluated changes in C statistic, the net reclassification improvement, and the integrated discrimination improvement to determine whether the addition of preoperative uric acid improved prediction of AKI. Of the 2,185 patients, 787 (36.0%) developed AKI. Preoperative uric acid was significantly associated with postoperative AKI (odds ratio, 1.18; 95% confidence interval, 1.10-1.26; P<0.001). Adding uric acid levels improved the C statistic and had significant impact on risk reclassification and integrated discrimination for AKI. Preoperative uric acid is related to postoperative AKI and improves the predictive ability of AKI. This finding suggests that preoperative measurement of uric acid may help stratify risks for AKI in in patients undergoing CABG.

Role of low- and high-frequency oscillations in the human hippocampus for encoding environmental novelty during a spatial navigation task.

The hippocampus plays a key role in the encoding and retrieval of information related to novel environments during spatial navigation. However, the neural basis for these processes in the human hippocampus remains unknown because it is difficult to directly measure neural signals in the human hippocampus. This study investigated hippocampal neural oscillations involved in encoding novel environments during spatial navigation in a virtual environment. Seven epileptic patients with implanted intracranial hippocampal depth electrodes performed three sessions of virtual environment navigation. Each session consisted of a navigation task and a location-recall task. The navigation task consisted of eight blocks, and in each block, the participant navigated to the location of four different objects and was instructed to remember the location of the objects. After the eight blocks were completed, a location-recall task was performed for each of the four objects. Intracranial electroencephalography data were monitored during the navigation tasks. Theta (5-8 Hz) and delta (1-4 Hz) oscillations were lower in the first block (novel environment) than in the eighth block (familiar environment) of the navigation task, and significantly increased from block one to block eight. By contrast, low-gamma (31-50 Hz) oscillations were higher in the first block than in the eighth block of the navigation task, and significantly decreased from block one to block eight. Comparison of sessions with high recall performance (low error between identified and actual object location) and low recall performance revealed that high-gamma (51-100 Hz) oscillations significantly decreased from block one to block eight only in sessions with high recall performance. These findings suggest that delta, theta, and low-gamma oscillations were associated with encoding of environmental novelty and high-gamma oscillations were important for the successful encoding of environmental novelty.

Effect of Helicobacter pylori eradication on metachronous recurrence after endoscopic resection of gastric neoplasm.

OBJECTIVES: Although many epidemiologic studies have shown that Helicobacter pylori (H. pylori) eradication has prophylactic effects on gastric cancer, their results are less clear in high-risk populations. We conducted this study to examine whether H. pylori eradication would affect the occurrence of metachronous gastric cancer after endoscopic resection in patients with early gastric cancer. METHODS: We retrospectively analyzed 2,089 adults who underwent endoscopic resection of gastric low-grade neoplasia, high-grade neoplasia, or differentiated invasive neoplasia from 2004 to 2008 at Asan Medical Center. Of these, a total of 1,007 patients with early gastric cancer were enrolled in this study. We evaluated the demographic data, the pathology, and the incidence of metachronous recurrence by dividing them into three groups: those without active H. pylori infection (Hp negative group, n=340), those who successfully underwent H. pylori eradication (eradicated group, n=485), and those who failed or did not undergo H. pylori eradication (noneradicated group, n=182). RESULTS: Metachronous recurrence was diagnosed in 75 patients, including 17 in the Hp, 34 in the eradicated, and 24 in the noneradicated groups. Median time to metachronous recurrence was 18 months (range, 7-75 months). The incidence of metachronous gastric cancer was 10.9 cases per 1,000 person-years in the Hp negative group, 14.7 cases per 1,000 person-years in the eradicated group, and 29.7 cases per 1,000 person-years in the noneradicated group. The hazard ratios in the noneradicated group compared with the Hp negative and eradicated groups were 2.5 (P<0.01) and 1.9 (P=0.02), respectively. H. pylori eradication reduced metachronous recurrence of gastric neoplasm, which was also shown in the secondary analysis of 1,487 patients with low-grade neoplasia and early gastric cancer. CONCLUSIONS: Successful H. pylori eradication may reduce the occurrence of metachronous gastric cancer after endoscopic resection in patients with early gastric cancer.

Association between C-reactive Protein and type of coronary arterial plaque in asymptomatic patients: assessment with coronary CT angiography.

PURPOSE: To determine whether C-reactive protein is associated with the type of coronary plaque seen at computed tomographic (CT) angiography. MATERIALS AND METHODS: The institutional review board approved this retrospective study, and the need for informed consent was waived. C-reactive protein levels were measured in 2653 asymptomatic subjects (mean age ± standard deviation, 54.7 years ± 9.2; 1811 men) who underwent self-referred coronary CT angiography as part of a general health checkup. The presence of coronary plaque, plaque type (calcified, mixed calcified, or noncalcified), stenosis degree, and number of involved segments were evaluated. Subjects with one type of plaque (calcified plaque, mixed plaque, and noncalcified plaque groups) and two or more types of plaque (multiple lesions group) were analyzed separately. Multivariate logistic regression analysis was used to evaluate the association between increasing C-reactive protein levels and plaque type. RESULTS: Coronary plaque was found in 1150 of the 2653 subjects (43.3%): calcified plaque (n = 604, 22.8%), mixed plaque (n = 67, 2.5%), noncalcified plaque (n = 208, 7.8%), and multiple lesions (n = 271, 10.2%). The C-reactive protein cutoff value of the fourth quartile was 1.2 mg/L (11.4 nmol/L), and all types of coronary plaque were increased in the higher quartile of the C-reactive protein levels. Multivariate logistic regression analysis showed that a higher C-reactive protein level was an independent predictor for the presence of noncalcified plaque (fourth vs first quartile group, odds ratio = 1.70, P = .025) and significant (50% and higher) coronary stenosis (odds ratio = 1.76, P = .020) after adjustment for traditional risk factors for coronary artery disease. CONCLUSION: C-reactive protein is associated with noncalcified coronary arterial plaque, as seen at coronary CT angiography in asymptomatic patients after adjustment for traditional risk factors.

Treatment and survival of patients with occult breast cancer with axillary lymph node metastasis: a nationwide retrospective study.

BACKGROUND AND OBJECTIVES: Occult breast cancer (OBC) accounts for 0.3-1.0% of all breast cancers and is a rare presentation of the disease. The present retrospective study examined the overall survival and prognostic factors associated with OBC in Korea. METHOD: The study included 142 OBC patients identified from the Korean Breast Cancer Society cancer registry from January 1990 to December 2009. All patients had pathologically positive axillary lymph nodes (N1-N3) and pathologically and radiologically negative in-breast lesions (T0/Tx) based on a retrospective review of the database. RESULTS: No statistically significant differences in overall survival were observed between patients undergoing axillary lymph node dissection (ALND) only (80.8%), breast conserving surgery (BCS) with ALND (98.0%), and mastectomy with ALND (92.5%) with P-value of 0.061. Nodal status was a significant prognostic factor (P = 0.004) on univariate analysis. When compared with T1 patients group, T0/TxN1 patients showed better survival than T1N1 patients (hazard ratio [HR] 0.253; 95% confidence interval, 0.104-0.618; P = 0.003), but T0/TxN2, T0/TxN3 patients showed similar survival to T1N2, T1N3 patients. CONCLUSIONS: OBC patients treated with ALND only showed comparable outcomes to those undergoing ALND combined with BCS or mastectomy. Nodal status may be an independent predictor of poor outcome in OBC patients.

Clinical significance of intensive endoscopic screening for synchronous esophageal neoplasm in patients with head and neck squamous cell carcinoma.

OBJECTIVES: Patients with head and neck squamous cell carcinoma (HNSCC) often develop second primary tumors in the upper aerodigestive tract. Early detection of synchronous esophageal squamous cell neoplasm (ESCN) is important because the prognosis of HNSCC can be affected by the statuses of second primary tumors. METHODS: In a prospective study, 308 patients with HNSCC were screened for synchronous ESCN between May 2010 and April 2012. All patients underwent conventional white-light endoscopic examination with Lugol chromoendoscopy and narrow band image. RESULTS: The median age was 61 years (range, 26-87 years), and the male-to-female ratio was 4.2:1. Two hundred and thirty-four patients (76.0%) were current or ex-smokers, 207 patients (67.2%) had a history of alcohol consumption and 56 patients (18.2%) had previous history of cancer. Synchronous ESCN was detected in 22 patients (7.1%), and most patients were at an early stage. The locations of index HNSCC in these patients were as follows: hypopharynx (n = 12), larynx (n = 6), oropharynx (n = 2) and oral cavity (n = 2). Synchronous ESCN was detected in 25.5% (12/47) of hypopharyngeal cancer and in 27.8% (15/54) of HNSCC involving the pyriform sinus. Multivariate analysis showed that smoking (current smoker vs. never smoker, Odds Ratio [OR] 8.3, p = 0.028), a history of cancer (OR 5.0, p = 0.002) and pyriform sinus involvement (OR 9.2, p < 0.0001) increased the risk of developing synchronous ESCN. CONCLUSIONS: Patients with HNSCC, especially those who are current smokers, have a history of cancer and have pyriform sinus involvement, should undergo intensive endoscopic screening to detect synchronous ESCN.

Pneumonia after endoscopic resection for gastric neoplasm.

BACKGROUND: Pneumonia following endoscopic procedures may affect the clinical course and prolong hospital stay. AIM: To investigate the incidence and risk factors for pneumonia after endoscopic resection (ER) for gastric neoplasm. METHODS: Subjects who underwent ER for gastric neoplasm at the Asan Medical Center from January 1997 to March 2013 were included. To investigate risk factors, control patients were randomly selected from these subjects. RESULTS: Of the 7,149 subjects who underwent ER for gastric neoplasm, 44 (0.62 %) developed pneumonia. The median age of these 44 patients was 68 years (range 31-82 years), and the male to female ratio was 3:1. Twenty-five of the pneumonia patients (56.8 %) were smokers, and 8 (18.2 %) had underlying pulmonary diseases. The median procedure time was 23 min (range 2-126 min), and pathologic diagnoses included adenocarcinoma (n = 29), dysplasia (n = 10), and hyperplastic polyp (n = 5). Compared with the control group, smoking (current smoker vs. never smoker, odds ratio [OR] 2.366, p = 0.021), total procedure time (OR 1.011, p = 0.048), and hemostasis time (OR 1.026, p = 0.028) were risk factors for the development of pneumonia. In multivariate analysis, age >65 years (OR 2.073, p = 0.031), smoking (current smoker vs. never smoker, OR 2.324, p = 0.023), and hemostasis time (OR 1.025, p = 0.038) were independent risk factors. All patients recovered from pneumonia, and the duration of hospital stay did not differ between patients with pneumonia and the control group (p = 0.077). CONCLUSIONS: Whereas old age, smoking, and longer hemostasis time are risk factors for pneumonia, its incidence after ER is not associated with clinically significant adverse outcomes.