National health screening may reduce cardiovascular morbidity and mortality among the elderly.

OBJECTIVES: Since 2007, the Korean government has provided a free health screening to the elderly starting at the age of 66 years. The purpose of this study was to evaluate the association between this general health screening and the incidences of stroke and myocardial infarction and mortality. STUDY DESIGN: The study design used in this study is a retrospective cohort study. METHODS: The study was conducted using the universe of insurance claims data of Korea and followed a cohort of individuals aged 66 years in 2009 from 2006 through 2016 (n = 354,194). We assessed the association between receipt of the national health screening and health outcomes using propensity matching and Cox proportional hazard models. RESULTS: We found that the receipt of the national health screening was associated with a reduction in negative health outcomes. The hazard ratio for stroke was 0.89 (P < 0.001), 0.88 (P < 0.001) for myocardial infarction and 0.58 for death (P < 0.001). CONCLUSION: Korea's national health screening was associated with reductions in cardiovascular morbidity and mortality in the elderly.

The effect of low body mass index on the development of chronic obstructive pulmonary disease and mortality.

BACKGROUND: Sarcopenia may worsen disease progression and lead to poor outcomes in chronic obstructive pulmonary disease (COPD). OBJECTIVES: We aimed to determine the effect of BMI on the development of COPD and mortality. METHODS: We enrolled 437 584 participants registered in the physical health check-up cohort database of the Korean National Health Interview Survey from 2002 to 2003, and we defined COPD diagnosis based on the ICD-10 code and prescribed medication. BMI (kg m-2 ) classified them to five groups (low BMI < 18.5, normal BMI 18.5-23, overweight 23-25, obesity 25-30, severe obesity ≥30) at baseline. RESULTS: Participants in the low BMI group had a significantly higher rate of COPD development for 13 years (7.6%) than those in other groups (3.4-4.1%, P < 0.0001). Amongst never or light smokers, COPD development in the low BMI group (5.6-6.7%) was significantly higher than that in other groups (2.8-4.7%). Similarly, amongst participants with a smoking history of ≥30 years, COPD development in the low BMI group (20.1%) was higher than those in other groups (8.4-12.4%). On multivariable analysis, normal or higher than normal body weight was significantly protective against the development of COPD (hazard ratio [HR], 0.609-0.739,) compared to low BMI. COPD-free-survival (HR, 0.491-0.622) and overall survival (HR, 0.440-0.585) were also better in them compared to those with low BMI (all P < 0.0001). CONCLUSIONS: Low BMI is an important risk factor for COPD development and mortality. Maintaining adequate body weight may reduce the risk for COPD development and mortality.

Effects of anti-osteoporosis medications on radiological and clinical results after acute osteoporotic spinal fractures: a retrospective analysis of prospectively designed study.

Effects of anti-osteoporosis medications such as anti-resorptive and anabolic agents on healing of osteoporotic spinal fracture were retrospectively investigated. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented good pain relief. These findings suggest that proper selection of medication could improve initial management of acute osteoporotic spinal fractures (OSFs). INTRODUCTION: Although anti-osteoporosis medications have beneficial effects on prevention of osteoporotic spinal fractures (OSFs), few studies have compared effects of medications on fracture healing following OSFs. Therefore, the purpose of this study was to elucidate the effects of different anti-osteoporosis medications on radiological and clinical outcomes after acute OSFs. METHODS: A total of 132 patients diagnosed with acute OSFs were enrolled and allocated into three groups [group I (n = 39, no anti-osteoporosis medication), group II (n = 66, bisphosphonate), and group III (n = 27, parathyroid hormone (PTH)]. Radiological parameters including magnetic resonance (MR) classification, occurrence of intravertebral cleft (IVC), and clinical outcomes such as numerical rating scale (NRS) and Oswestry disability index were assessed. Risk analyses for IVC and progressive collapse were done along the related factors and medication type. RESULTS: IVC sign was observed in 30 patients. The rate of IVC sign was lower in group III (7.4%) than that in group I (20.5%) or group II (30.3%), although the difference was not statistically significant. Moreover, the degree of NRS improvement was better in group III than that in group I or group II (5.7 vs. 3.1 vs. 3.5, p < 0.001). On multiple regression analysis, mid-portion type fracture in MR classification was a significant risk factor for progressive OSFs. The use of PTH showed significant lower incidences of occurrence of IVC (odds ratio (OR) = 0.160) and increase in height loss (OR = 0.325). CONCLUSIONS: Different anti-osteoporosis medications presented different clinical and radiological results after acute OSFs. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented better clinical outcomes. Proper selection of medication might improve initial management of acute OSFs.

Zoomed MRI Guided by Combined EEG/MEG Source Analysis: A Multimodal Approach for Optimizing Presurgical Epilepsy Work-up and its Application in a Multi-focal Epilepsy Patient Case Study.

In recent years, the use of source analysis based on electroencephalography (EEG) and magnetoencephalography (MEG) has gained considerable attention in presurgical epilepsy diagnosis. However, in many cases the source analysis alone is not used to tailor surgery unless the findings are confirmed by lesions, such as, e.g., cortical malformations in MRI. For many patients, the histology of tissue resected from MRI negative epilepsy shows small lesions, which indicates the need for more sensitive MR sequences. In this paper, we describe a technique to maximize the synergy between combined EEG/MEG (EMEG) source analysis and high resolution MRI. The procedure has three main steps: (1) construction of a detailed and calibrated finite element head model that considers the variation of individual skull conductivities and white matter anisotropy, (2) EMEG source analysis performed on averaged interictal epileptic discharges (IED), (3) high resolution (0.5 mm) zoomed MR imaging, limited to small areas centered at the EMEG source locations. The proposed new diagnosis procedure was then applied in a particularly challenging case of an epilepsy patient: EMEG analysis at the peak of the IED coincided with a right frontal focal cortical dysplasia (FCD), which had been detected at standard 1 mm resolution MRI. Of higher interest, zoomed MR imaging (applying parallel transmission, 'ZOOMit') guided by EMEG at the spike onset revealed a second, fairly subtle, FCD in the left fronto-central region. The evaluation revealed that this second FCD, which had not been detectable with standard 1 mm resolution, was the trigger of the seizures.

Analysis and comparison of the cost-effectiveness of statins according to the baseline low-density lipoprotein cholesterol level in Korea.

WHAT IS KNOWN AND OBJECTIVE: There are a few Korean studies on the economics of statins based on reduction in low-density lipoprotein cholesterol (LDL-C) data from other countries. This study aimed to analyse and compare the cost-effectiveness of statins according to the baseline LDL-C level in Korea. METHODS: Between January 2009 and December 2015, the data of patients who were prescribed statins for the first time were extracted from electronic medical records. We performed a cost-effectiveness analysis (CEA) based on the LDL-C reduction rate (CEA-RR) and target achievement rate. RESULTS AND DISCUSSION: Among high-intensity statins, the CEA-RR value of rosuvastatin (20 mg) was significantly lower than that of atorvastatin (40 mg) at all baseline LDL-C levels, except levels of 160-189 mg/dL. Additionally, at baseline LDL-C levels of 130-159 mg/dL, the CEA-RR value of rosuvastatin (20 mg) was three times lower than that of atorvastatin (40 mg) (9·1 ± 2·5 $/% vs. 31·7 ± 15·0 $/%, P < 0·001). Among moderate-to-low-intensity statins, rosuvastatin (5 mg) showed the lowest CEA-RR value (4·0 ± 0·6 $/%), and the value significantly increased for pitavastatin (2 mg) (8·0 ± 0·6 $/%), atorvastatin (10 mg) (9·5 ± 0·5 $/%), simvastatin (10·8 ± 1·1 $/%) and pravastatin (40 mg) (11·5 ± 0·9 $/%) in order (P < 0·0001). On changing from atorvastatin (10 mg) to atorvastatin (20 mg), the additional yearly cost was 16·0 and additional CEA-RR value was 2·74 $/%. On the other hand, on changing from atorvastatin (10 mg) to rosuvastatin (10 mg), the additional yearly cost was -16·3 and additional CEA-RR value was -1·8 $/%. WHAT IS NEW AND CONCLUSION: We successfully compared the cost-effectiveness of statins according to the baseline LDL-C level in Korea. It is expected that our findings will help clinical decision-making with regard to statin prescription, and this will help reduce national medical expenditure.

UTE-ΔR2 -ΔR2 * combined MR whole-brain angiogram using dual-contrast superparamagnetic iron oxide nanoparticles.

The ability to visualize whole-brain vasculature is important for quantitative in vivo investigation of vascular malfunctions in cerebral small vessel diseases, including cancer, stroke and neurodegeneration. Transverse relaxation-based ΔR2 and ΔR2 * MR angiography (MRA) provides improved vessel-tissue contrast in animal deep brain with the aid of intravascular contrast agents; however, it is susceptible to orientation dependence, air-tissue interface artifacts and vessel size overestimation. Dual-mode MRA acquisition with superparamagnetic iron oxide nanoparticles (SPION) provides a unique opportunity to systematically compare and synergistically combine both longitudinal (R1 ) and transverse (ΔR2 and ΔR2 *) relaxation-based MRA. Through Monte Carlo (MC) simulation and MRA experiments in normal and tumor-bearing animals with intravascular SPION, we show that ultrashort TE (UTE) MRA acquires well-defined vascularization on the brain surface, minimizing air-tissue artifacts, and combined ΔR2 and ΔR2 * MRA simultaneously improves the sensitivity to intracortical penetrating vessels and reduces vessel size overestimation. Consequently, UTE-ΔR2 -ΔR2 * combined MRA complements the shortcomings of individual angiograms and provides a strategy to synergistically merge longitudinal and transverse relaxation effects to generate more robust in vivo whole-brain micro-MRA. Copyright © 2016 John Wiley & Sons, Ltd.

Computed tomography findings associated with bacteremia in adult patients with a urinary tract infection.

The use of computed tomography (CT) in the diagnosis of urinary tract infection (UTI) has rapidly increased recently at acute stage, but the CT findings associated with bacteremia in UTI patients are unknown. 189 UTI patients were enrolled who underwent a CT scan within 24 h after hospital admission. We classified CT findings into eight types: a focal or multifocal wedge-shaped area of hypoperfusion, enlarged kidneys, perinephric fat stranding, ureteritis or pyelitis, complicated renal cyst, renal papillary necrosis, hydronephrosis, and renal and perirenal abscess. A retrospective analysis was conducted to evaluate the CT findings associated with bacteremia. The mean age of these patients was 60 ± 17.2 years, and 93.1 % were women. Concurrent bacteremia was noted in 40.2 % of the patients. Abnormal CT findings were noted in 96.3 % of the patients and 62.4 % had two or more abnormal findings. The most frequent abnormal CT finding was a focal or multifocal wedge-shaped area of hypoperfusion (77.2 %), followed by perinephric fat stranding (29.1 %). Perinephric fat stranding, hydronephrosis, and the presence of two or more abnormal CT findings were significantly associated with bacteremia in patients with community-acquired UTI. In the multivariate logistic regression analysis, age [odds ratio (OR) 1.03; 95 % confidence interval (CI) 1.009-1.062], two or more abnormal CT findings (OR 3.163; 95 % CI 1.334-7.498), and hydronephrosis (OR 13.160; 95 % CI 1.048-165.282) were significantly associated with bacteremia. Physicians should be aware that appropriate early management is necessary to prevent fatality in patients with these CT findings.

Comparative analysis of the efficacy of omega-3 fatty acids for hypertriglyceridaemia management in Korea.

WHAT IS KNOWN AND OBJECTIVE: This study aimed to compare the ability of statin monotherapy (ST group), omega-3 fatty acid monotherapy (OM_A group) and combination therapy with omega-3 fatty acids and a statin (OM_S group), to reduce triglyceride (TG) levels in patients with hypertriglyceridaemia. METHODS: In this retrospective cohort study, we extracted data from the electronic medical records of patients initially prescribed either a statin or omega-3 fatty acids between January, 2009 and December, 2013. We performed a comparative analysis of the change in cholesterol levels between baseline and an average of 3 months later. RESULTS AND DISCUSSION: Data were extracted for 2071 patients. The average daily eicosapentaenoic acid (EPA) ethyl ester and docosahexaenoic acid (DHA) ethyl ester intake was 1689 mg, and 79-86% of the OM_A and OM_S groups were prescribed two omega-3 fatty acid capsules. At a baseline TG level of between 200 and 500 mg/dL, TG levels were reduced by 16 ± 2·8% in the ST group, 28 ± 2·8% in the OM_A group and 29 ± 2·3% in the OM_S group (P = 0·001 for ST group vs. OM_A and OM_S groups), with no difference between the OM_A and OM_S groups. At a baseline TG level ≥500 mg/dL, there was no difference in TG level reduction between the three groups (54 ± 7·3%, 55·8 ± 3·5% and 51·8 ± 6·8%, respectively, P = 0·851). WHAT IS NEW AND CONCLUSION: Although omega-3 fatty acids are not considered the primary medication for hypertriglyceridaemia, the prescription of omega-3 fatty acids is justifiable if reduction in TG levels is judged to be necessary.

Analysis and comparison of statin prescription patterns and outcomes according to clinical department.

WHAT IS KNOWN AND OBJECTIVE: There is a disparity between the Korean treatment guidelines and actual clinical prescription habits. This study was designed to evaluate the department-specific disparities and achievement rates for low-density lipoprotein cholesterol (LDL-C) targets, based on each department's specific statin prescription patterns. METHODS: We retrospectively evaluated data from 31 718 patients who had been prescribed a statin at least once between January 2008 and June 2013 at our institution. Patients were classified into the high-risk (target LDL-C < 100 mg/dL) or moderate-risk (target LDL-C < 130 mg/dL) groups, according to the National Cholesterol Education Programme-Adult Treatment Panel III guidelines. RESULTS AND DISCUSSION: Statins were most commonly prescribed in the cardiology (32·0%) and endocrinology (26·6%) departments. For the high-risk group, 70% of patients in the cardiology, endocrinology and cardiac surgery departments achieved their target LDL-C levels (<100 mg/dL). However, the target achievement rates in most other departments were <70%. For the moderate-risk group, 79·2% of patients achieved their target levels. Departments that prescribed a greater number of high- or intermediate-potency statins were more likely to achieve their target LDL-C levels. The group that achieved their target LDL-C levels (<100 mg/dL) exhibited a significant positive relationship (Spearman's correlation coefficient = 0·8571, P = 0·0065), from low to high potency. WHAT IS NEW AND CONCLUSION: Some departments tend to undertreat when prescribing statins. However, to reach to the target LDL-C levels, physicians must overcome their tendency to undertreat with statins. We believe that the target achievement rate will increase if doctors are more actively aware of a patient's individual status and related risk factors before prescribing statins.

Statin-related aminotransferase elevation according to baseline aminotransferases level in real practice in Korea.

WHAT IS KNOWN AND OBJECTIVE: Higher rate of statin-related hepatotoxicity has been reported for Koreans than for Westerners. Moreover, statin-related aminotransferase elevation for those who show borderline levels of aspartate transaminase (AST) and alanine transaminase (ALT) (≤×3 of UNL) at baseline has not been fully investigated. METHODS: Post-statin changes AST/ALT levels during the first year for 21 233 Korean outpatients at two large academic teaching hospitals from January 2009 to December 2013 were analysed using electronic health record data. The date of the first statin prescription was set as baseline. We also performed a comparative analysis of statin-related AST/ALT elevations according to the type of statin, followed by an analysis of clinical risk factors. RESULTS AND DISCUSSION: The progression rate to abnormal AST/ALT values [>×3 the upper normal limit (UNL)] was significantly higher (2·4-16% vs. 0·3-1·7%, P < 0·001) in subjects with borderline (>×1, but ≤×3 of UNL) compared with normal AST/ALT values at baseline. Those with normal baseline AST/ALT did not show significantly different progression rate between different statin medications (P = 0·801). However, patients taking pitavastatin (HR = 0·76, P = 0·657) were least likely to develop abnormal AST/ALT, whereas those taking fluvastatin (HR = 2·96, P = 0·029) were the most likely to develop abnormal AST/ALT compared with atorvastatin for patients who were with baseline borderline AST/ALT. However, given the small sample sizes and the observational nature of our study, these need further study. WHAT IS NEW AND CONCLUSION: It is advisable to regularly monitor AST/ALT levels even in patients with AST/ALT increases >×1. Future studies should aim to determine the possible risk factors for each specific statin type by analysing various confounding variables.

Robust MR assessment of cerebral blood volume and mean vessel size using SPION-enhanced ultrashort echo acquisition.

Intravascular superparamagnetic iron oxide nanoparticles (SPION)-enhanced MR transverse relaxation rates (∆R2(⁎) and ∆R2) are widely used to investigate in vivo vascular parameters, such as the cerebral blood volume (CBV), microvascular volume (MVV), and mean vessel size index (mVSI, ∆R2(⁎)/∆R2). Although highly efficient, regional comparison of vascular parameters acquired using gradient-echo based ∆R2(⁎) is hampered by its high sensitivity to magnetic field perturbations arising from air-tissue interfaces and large vessels. To minimize such demerits, we took advantage of the dual contrast property of SPION and both theoretically and experimentally verified the direct benefit of replacing gradient-echo based ∆R2(⁎) measurement with ultra-short echo time (UTE)-based ∆R1 contrast to generate the robust CBV and mVSI maps. The UTE acquisition minimized the local measurement errors from susceptibility perturbations and enabled dose-independent CBV measurement using the vessel/tissue ∆R1 ratio, while independent spin-echo acquisition enabled simultaneous ∆R2 measurement and mVSI calculation of the cortex, cerebellum, and olfactory bulb, which are animal brain regions typified by significant susceptibility-associated measurement errors.

The TLR4-associated phospholipase D1 activation is crucial for Der f 2-induced IL-13 production.

BACKGROUND: House dust mites (HDMs) are the most important source of indoor aeroallergens that contribute to the rising incidence of allergic diseases such as allergic asthma. The major HDM, Der f 2, induces inflammatory cytokine expression. Little is known about the signaling pathway involved. OBJECTIVE: We wanted to define the Der f 2 signaling pathway from its receptor to the transcription factor responsible for IL-13 expression and production. METHODS: Human bronchial epithelial cells were stimulated with Der f 2. The release and gene expression of IL-13 were measured by means of ELISA and RT-PCR, respectively. In the airway inflammation mouse model, airway responses were assessed using ELISA, histology, BAL fluid, and methacholine responsiveness. RESULTS: Here, we show that Der f 2 binds to TLR4 and induces IL-13 expression and production. In the airway inflammation mouse model, Der f 2-induced IL-13 production significantly decreased with treatment of TAK-242, a novel TLR4 inhibitor. Activation of TLR4 by Der f 2 requires the recruitment and activation of Syk, which leads to phosphorylation of PLCγ and membrane translocation of PKCα. p38 MAPK is then activated by PKCα and stimulates PLD1 activity by phosphorylating the Thr147 residue of PLD1. PLD1 activation enhanced binding of ROCK1 to ATF-2 and leads to increased expression of IL-13. CONCLUSION: Our data extend the knowledge for a variety of possible roles of PLD1 in allergic disorders including asthma pathogenesis and suggest possible candidacy of PLD1 as a molecular target for novel therapeutic approaches.

The optimal morning:evening ratio in total dose of twice-daily biphasic insulin analogue in poorly controlled Type 2 diabetes: a 24-week multi-centre prospective, randomized controlled, open-labelled clinical study.

AIMS: Biphasic insulin analogues are widely used in patients with Type 2 diabetes mellitus suboptimally controlled on oral anti-diabetic drugs. Several topics in this area remain controversial, including how to divide the daily dose of biphasic insulin analogue. We aimed to determine the optimal dosing ratio of twice-daily biphasic insulin analogue and to compare the glycaemic efficacy among groups of patients using different initial dosing ratios of biphasic insulin analogue. METHODS: A total of 100 poorly controlled insulin-naive subjects with Type 2 diabetes [HbA1c ≥ 58 mmol/mol, (7.5%)] on oral anti-diabetic drugs were randomized into three groups according to initial morning:evening dosing ratio (group I, 50:50; group II, 55:45; group III, 60:40) of twice-daily biphasic insulin analogue (biphasic insulin aspart 70/30, biphasic insulin aspart 30). The primary outcome measure was the difference in pre-breakfast to pre-dinner dose ratio at the end of the study. RESULTS: Twice-daily biphasic insulin analogue showed a significant improvement in glycaemic control [HbA1c from 70 mmol/mol (8.6%) to 60 mmol/mol (7.6%)] after 24 weeks regardless of the initial dose ratio given. Despite the similar efficacy and safety profiles among three groups, morning dose was significantly increased (from 50:50 to 55:45-60:40) in group I after 24 weeks. However, there was no significant change in splitting ratio in groups II and III (with higher morning dose) over the 24-week treatment period. CONCLUSIONS: These results indicate that initiating twice-daily biphasic insulin analogue on regimens with a higher dose before breakfast than before dinner (i.e. ratio approximately 55:45 to 60:40) might be more appropriate in Korean subjects with Type 2 diabetes.

Costs of illness and quality of life in patients with systemic lupus erythematosus in South Korea.

OBJECTIVE: To assess the costs of illness, health-related quality of life (HRQOL) and their associated factors in patients with systemic lupus erythematosus (SLE) in South Korea. METHOD: Two hundred and one patients with SLE were enrolled at the Rheumatology clinic of Seoul National University Hospital. Direct, indirect and total costs and HRQOL were measured using hospital electronic data and face-to-face interview. Socio-demographic and clinical factors associated with cost of illness and HRQOL were analyzed using multiple regression and multivariate logistic regression. RESULTS: The average total cost of illness was estimated to be KRW 9.82 million (US $ 8993) per year, of which 41.6% was accounted for by direct costs and 58.4% by indirect costs. In multivariate regression, patients with renal involvement and those with depression incurred an average increment in annual total costs of 37.6% (p = 0.050) and 49.1% (p = 0.024), respectively, and an average increment in annual direct costs of 26.4% (p = 0.050) and 43.3% (p = 0.002), respectively, compared with patients without renal involvement and depression, respectively. In addition, disease damage was positively associated with an average increment in annual total and direct costs (55.3%, p = 0.006; 33.3%, p = 0.013, respectively), and the occurrence of indirect costs (OR 2.21, 1.09-4.88). There was no significant difference in HRQOL between patients with and without renal involvement (0.655 vs. 0.693, p = 0.203) CONCLUSION: Renal involvement, depression, and disease damage were major factors associated with higher total and medical costs for patients with SLE in South Korea. Effective treatment of renal disorders and depression may reduce the high economic burden of SLE.

Rhabdomyolysis associated with cytomegalovirus infection in kidney transplant recipients.

Rhabdomyolysis is a pathological syndrome caused by skeletal muscle cell damage that affects the integrity of the cellular membrane and leads to the release of toxic intracellular constituents into the bloodstream. Although cytomegalovirus (CMV) has rarely been reported as a cause of rhabdomyolysis, CMV infection could be considered as a possible cause because of its clinical significance in kidney transplant recipients (KTRs). We report 2 cases of rhabdomyolysis associated with CMV infection in KTRs. A 64-year-old woman (Case 1) and a 65-year-old man (Case 2), who had each received a kidney from a living unrelated donor, were admitted with complaints of weakness in both legs and myalgia. Laboratory findings revealed highly increased creatine phosphokinase and myoglobinuria. In both cases, no recent alterations of medications had occurred, and other causes of rhabdomyolysis--such as trauma, alcohol, drugs, and electrolyte abnormalities - were excluded. CMV pp65 antigen was positive, and patients were diagnosed with rhabdomyolysis associated with CMV infection. Both patients recovered without complications after ganciclovir treatment. In conclusion, CMV infection should be considered as a possible cause of rhabdomyolysis in KTRs.

Successful withdrawal of antiviral treatment in kidney transplant recipients with chronic hepatitis B viral infection.

BACKGROUND: The optimal duration of antiviral therapy for kidney transplant recipients (KTR) with chronic hepatitis B virus (HBV) infection remains unclear. We reported the long-term outcomes after withdrawal of antiviral agent in KTR with chronic HBV infection. METHODS: We retrospectively investigated the hepatitis B surface antigen (HBsAg)-positive KTR with antiviral agents between January 2002 and January 2012. Antiviral treatments were withdrawn in patients who met all of the following 7 criteria: (i) no clinical and histologic evidence of cirrhosis, (ii) normal liver biochemistry, (iii) negative for both HBV DNA and hepatitis B envelope antigen (HBeAg), (iv) no resistance to antiviral agent, (v) antiviral therapy > 9 months, (vi) maintenance dosage of immunosuppressant for > 3 months, and (vii) no history of acute rejection during recent 6 months. All patients were followed regularly at approximately 3-6 months for liver enzyme, viral markers, and HBV DNA level after antiviral withdrawal. RESULTS: Among a total of 445 KTR, 14 HBsAg-positive patients were included in this study. Antiviral agents were used, with lamivudine in 11 patients, and with adefovir, entecavir, and telbivudine in 3 patients, respectively. Discontinuation of antiviral agent was attempted in 6 (42.9%) of 14 patients who satisfied the criteria. The median duration of antiviral therapy before withdrawal was 14.3 months (range, 9-24 months). Four (66.7%) of 6 patients were successfully withdrawn and remained negative for HBV DNA for a median 60.5 months (range, 47-82 months). The baseline HBV DNA level was not related to maintenance of remission after withdrawal. Two reactivated patients resumed antiviral treatment immediately, with subsequent normalization of HBV DNA. During the follow-up, 1 patient developed hepatocellular carcinoma; however, no patient death or graft failure was reported for all HBsAg-positive KTR. CONCLUSIONS: Antiviral therapy can be discontinued successfully and safely in selected KTR with chronic HBV infection, after complete suppression of HBV and sufficient duration of antiviral therapy.

Effects of lactulose supplementation on performance, blood profiles, excreta microbial shedding of Lactobacillus and Escherichia coli, relative organ weight and excreta noxious gas contents in broilers.

This study was to evaluate the effects of lactulose supplementation on performance, blood profiles, excreta microbial shedding of Lactobacillus and Escherichia coli, relative organ weight and excreta noxious gas contents in broilers. A total of 720 ROSS 308 broilers with a body weight of 46 ± 0.1 g (1 day of age) were used in a 28-d experiment. Broilers were randomly allotted to 4 experiment diets with 12 replicate pens and 15 birds per pen. Dietary treatments were as follows: NC, negative control (without antibiotic); PC, NC + 0.1% tiamulin; L1, NC + 0.1% lactulose; and L2, NC + 0.2% lactulose. Broilers were fed with phase 1 (1-8 day), phase 2 (9-18 day) and phase 3 (19-28 day) diets in the form of mash. During day 1-8, broilers fed the PC and L2 diets had higher (p < 0.05) body weight gain than those fed the NC diet. During day 19-28, broilers fed the L1 and L2 diets had lower (p < 0.05) feed intake than those fed the NC diet. The feed conversion ratio (FCR) was decreased (p < 0.05) in L1 treatment compared with NC treatment. Overall, the FCR was improved (p < 0.05) in all supplementation treatments compared with NC treatment. The apparently metabolizable nitrogen in L1 treatment was higher (p < 0.05) than that in NC treatment at day 28. The excreta Lactobacillus was increased and E. coli was decreased in PC and L2 treatments compared with NC treatment at day 28 (p < 0.05). The excreta NH3, H2S and acetic acid contents were decreased (p < 0.05) in L1 and L2 treatments compared with NC treatment. The relative weight of abdominal fat of broilers fed the PC diet was lowest (p < 0.05) compared with other treatments. In conclusion, this study indicated that dietary supplementation of 0.1% or 0.2% lactulose could improve growth performance, decrease excreta E. coli and excreta NH3 and H2S contents.

Role of the superior turbinate when performing endoscopic endonasal transsphenoidal approach.

BACKGROUND: This study examined the relationship between the superior turbinate and natural ostium of the sphenoid sinus, as seen during the endoscopic endonasal transsphenoidal approach (EETSA) for sellar lesions and described how to enter the sphenoethmoid cell safely for complete exposure of the sellar floor, including adjacent vital structures such as the prominence of the optic nerve and carotid artery. MATERIALS AND METHODS: This study retrospectively reviewed the medical records and operative findings of 154 patients, who underwent EETSA between February 2009 and February 2011. We evaluated the location of the natural ostium of the sphenoid sinus relative to the superior turbinate and revealed the clinical significance of the superior turbinate as a surgical guide to enter into the sphenoethmoid cell during EETSA. RESULTS: The natural ostium of the sphenoid sinus was located medially to the posteroinferior end of the superior turbinate in 151 (98%) patients. In 1 patient, the natural ostia of the sphenoid sinus were located lateral to the superior turbinate bilaterally. Sphenoethmoid cell was encountered in 53 (34%) patients. We could easily enter the sphenoethmoid cell at the point where the superior turbinate was attached to the anterior wall of the sphenoid sinus. CONCLUSIONS: The superior turbinate is a good surgical landmark for identifying the natural ostium of the sphenoid sinus and as a guide for the surgical entrance to the sphenoethmoid cell extending to the sphenoid sinus during EETSA.

Effect of dietary supplementation of procyanidin on growth performance and immune response in pigs.

This study was performed to determine the effect of dietary supplementation of procyanidin on growth performance, blood characteristics, and immune function in growing pigs. In experiment 1 (Exp. 1), thirty-two crossbred pigs with an initial BW of 19.2±0.3 kg were allocated into 4 treatments for an 8-wk experiment: i) CON (basal diet), ii) MOS 0.1 (basal diet+0.1% mannanoligosaccharide), iii) Pro-1 (basal diet+0.01% procyanidin), and iv) Pro-2 (basal diet+0.02% procyanidin). Pigs fed Pro-1 and Pro-2 diets had greater (p<0.05) gain:feed ratio compared with those fed CON or MOS 0.1 diets. Serum creatinine concentration was less (p<0.05) in Pro-2 treatment than those in CON, MOS 0.1 and Pro-1 treatments. In Exp. 2, twelve pigs (BW 13.4±1.3 kg) received basal diet with i) 0 (CON), ii) 0.02% (Pro-0.02%), and iii) 0.04% procyanidin (Pro-0.04%) for 4 wk. Concentration of platelets was lower (p<0.05) in the Pro-0.04% group compared to CON at 24 h after lipopolysaccharide (LPS) challenge. In addition, secretion of cytokines from cultured peripheral blood mononuclear cells (PBMC) in the presence or absence of procyanidin was examined. The levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α were lower (p<0.05) in Pro (LPS-stimulated PBMCs+procyanidin) than those in CON (LPS-stimulated PBMCs+PBS) at 4 h after LPS challenge. These data suggest that dietary addition of procyanidin improves feed efficiency and anti-inflammatory cytokines of pigs.

Extended haplotype association study in Crohn's disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3.

The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn's disease (CD) compared with non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to CD etiology in this population, most notably at NOD2, in which three causal, uncommon and conditionally independent NOD2 variants reside on a shared background haplotype. We present an analysis of extended haplotypes that showed significantly greater association to CD in the Ashkenazi Jewish population compared with a non-Jewish population (145 haplotypes and no haplotypes with P-value <10(-3), respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established CD loci. We performed exome sequencing of 55 Ashkenazi Jewish individuals and follow-up genotyping focused on variants in these two regions. We observed Ashkenazi Jewish-specific nominal association at R755C in TRPM2 on chromosome 21. Within the chromosome 16 region, R642S of HEATR3 and rs9922362 of BRD7 showed genome-wide significance. Expression studies of HEATR3 demonstrated a positive role in NOD2-mediated NF-κB signaling. The BRD7 signal showed conditional dependence with only the downstream rare CD-causal variants in NOD2, but not with the background haplotype; this elaborates NOD2 as a key illustration of synthetic association.