Search

Background and Purpose: No established early biomarkers currently exist to predict responses during concurrent chemoradiotherapy (CCRT) in patients with unresectable non-small cell lung cancer (NSCLC). This study investigated the potential of gross tumor volume (GTV) and its changes during CCRT as predictors of survival outcomes., Materials and Methods: We identified 227 patients with unresectable stage III NSCLC who underwent definitive CCRT followed by durvalumab between November 2018 and December 2022. GTV was defined as the volume of the primary tumor, assessed at two time points: before starting CCRT for initial planning (GTV1), and at the fourth week of CCRT for adaptive planning (GTV2). Both relative and absolute regressions between GTV1 and GTV2 were calculated., Results: The median GTV1 volume was 90 mL (range, 5-840 mL), and the median GTV2 volume was 64 mL (range, 1-520 mL), resulting in median absolute and relative regressions of 18.6 mL and 25.0 %, respectively. Among the GTV parameters, relative GTV regression exhibited the strongest predictive value, with an area under the curve (AUC) of 0.804 for in-field progression and 0.711 for overall progression. The 1-year progression-free survival rates for the high (>30 %), intermediate (0-30 %), and low (≤0%) relative regression groups were 88.0 %, 62.6 %, and 14.3 %, respectively (p = 0.006 for high vs. intermediate; p < 0.001 for intermediate vs. low). Additionally, GTV2 volume demonstrated stronger associations with survival outcomes than GTV1 volume., Conclusion: Relative GTV regression was identified as a promising early predictor for patients with unresectable stage III NSCLC. Further development of a multi-parametric predictive model is warranted to guide patient-tailored therapeutic approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial., Objective: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia., Methods: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting β 2 -agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/μL; <300/μL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV 1 ) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56., Results: Of 695 patients randomized, 473 had baseline bEOS ≥300/μL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV 1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/μL, there were numerical improvements in AAER, pre-BD FEV 1 , and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population., Conclusions: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Nanshan Zhong reports financial support was provided by AstraZeneca. Kefang Lai reports financial support was provided by AstraZeneca. Dejun Sun reports financial support was provided by AstraZeneca. Ranran Dai reports financial support was provided by AstraZeneca. Ronnie Samoro reports financial support was provided by AstraZeneca. Hae-Sim Park reports financial support was provided by AstraZeneca. Annika Astrand reports a relationship with AstraZeneca that includes: employment and equity or stocks. David Cohen reports a relationship with AstraZeneca that includes: employment and equity or stocks. Maria Jison reports a relationship with AstraZeneca that includes: employment and equity or stocks. Vivian H Shih reports a relationship with AstraZeneca that includes: employment and equity or stocks. Viktoria Werkstrom reports a relationship with AstraZeneca that includes: employment and equity or stocks. Yuhui Yao reports a relationship with AstraZeneca that includes: employment and equity or stocks. Yajuan Zhang reports a relationship with AstraZeneca that includes: employment and equity or stocks. Wenying Zheng reports a relationship with AstraZeneca that includes: employment and equity or stocks. Tanya Jandu and Helen Brereton of inScience Communications, Springer Healthcare Ltd, UK, provided medical writing support, which was funded by AstraZeneca. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Aims: We investigated the association between diabetes status at admission and in-hospital outcomes in all hospitalized patients, regardless of the reason for admission., Methods: All individuals aged 20 years or older who were admitted to Yongin Severance Hospital between March 2020 and February 2022 were included in study. Subjects were categorized into three groups: non-DM, known DM, and newly diagnosed DM, based on medical history, anti-diabetic medications use, and laboratory test. Hospitalization-related outcomes, including in-hospital mortality and length of hospital stay, were compared between groups., Results: 33,166 participants were enrolled. At hospitalization, 6,572 (19.8 %) subjects were classified as known DM, and another 2,634 (7.9 %) subjects were classified as newly diagnosed DM. In-hospital mortality was highest in newly diagnosed DM (HR 1.89, 95% CI 1.58-2.26, p < 0.001) followed by known DM (HR 1.41, 95% CI 1.18-1.69, p < 0.001) compared to non-DM. Length of hospital stay was significantly longer in newly diagnosed DM (median [IQR] 9.0 [5.0-18.0],days) than known DM (median [IQR] 5.0 [3.0-10.0],days)(p < 0.001) and non-DM (median [IQR] 4.0 [2.0-7.0],days). After adjusting for multiple covariates, newly diagnosed diabetes was independently associated with increased in-hospital mortality (p < 0.001)., Conclusions: Diabetes status at admission was closely linked to hospitalization-related outcomes. Notably, individuals with newly diagnosed diabetes demonstrated a higher risk of in-hospital mortality and a prolonged length of hospital stay., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Little is known about the nature of relationships between sleep disturbance and influencing factors in rheumatoid arthritis. The purpose of this study was to identify factors that influence sleep disturbance and to evaluate mediating effects of depression on sleep disturbance. A nonexperimental, descriptive, correlational study design was adopted. One hundred patients with rheumatoid arthritis were recruited. Inflammatory status and levels of pain, fatigue, functional disability, depression, and sleep disturbance were measured. The factors that directly influenced sleep disturbance were gender, rheumatoid arthritis duration, serum C-reactive protein level, fatigue, and depression. Depression was found to have mediating effects on the relationships between sleep disturbance and arthritis symptoms. Pain, fatigue, and depression were found to have significant direct or indirect impacts on sleep disturbance. Our findings may improve understanding of sleep disturbance and aid the development of effective nursing management strategies for patients with rheumatoid arthritis suffering from sleep disturbance., (Copyright © 2022 by National Association of Orthopaedic Nurses.)

Background: We investigated the association between moderate-to-severe prostatitis-like symptoms and the predictors of benign prostatic hyperplasia (BPH) progression., Methods: Men who underwent health checkups were analyzed. We classified symptoms as "moderate to severe" if the pain score according to the National Institutes of Health-Chronic Prostatitis Symptoms Index was ≥8 and predictors of the progression of BPH were defined as having a prostate-specific antigen (PSA) ≥1.6 ng/mL, total prostate volume (TPV) ≥31 mL, international prostate symptom score (IPSS) ≥20, and maximal flow rate (Q max ) <10.6 mL/s. A total of 8368 patients formed the cohort for propensity score matching, including 445 men with moderate-to-severe prostatitis-like symptoms and 5390 men with no symptoms; ultimately, however, the propensity score of these groups matched at a 1:2 ratio., Results: After propensity matching, the two groups were evenly distributed with respect to age, International Index of Erectile Function-5 score, metabolic syndrome, and testosterone. The percentage of participants with ≥1 predictor for the progression of BPH, a TPV of ≥31 cm 3 , PSA levels of ≥1.6 ng/mL, Q max <10.6 mL/s, and IPSS ≥20 were all greater in men with moderate-to-severe prostatitis-like symptoms. There were significant differences in the percentage of participants with ≥1 predictor for the progression of BPH (30.6% vs. 58.0%; p < 0.001), Q max <10.6 mL/s (3.9% vs. 7.0%, p = 0.023), and IPSS ≥20 (9.6% vs. 44.7%, p < 0.001)., Conclusion: Moderate-to-severe prostatitis-like symptoms are significantly and independently associated with predictors of BPH progression., Competing Interests: The authors have no potential or financial conflicts of interests to declare., (© 2022 Asian Pacific Prostate Society. Publishing services by Elsevier B.V.)

Objective: Limited data are available regarding the rates and risk factors of severe to serious adverse reactions (ARs) to the ChAdOx1 nCoV-19 vaccine. Methods: Eligible participants were healthcare workers who received their first dose of the ChAdOx1 nCoV-19 vaccine in either of two university hospitals in Seoul, Korea. We evaluated the type and severity of ARs 7 days after the first dose of the ChAdOx1 nCoV-19 vaccine using a questionnaire survey delivered via a smartphone application link. Results: Among the 1,603 participants who completed the survey, 684 (42.7%) participants experienced any kind of grade 3 to grade 4 AR. Being young (adjusted odds ratio [OR] for age 21-30 years = 2.49, 95% confidence interval [CI] = 1.75-3.56; adjusted OR for 31-40 years = 1.78, 95% CI = 1.22-2.62; adjusted OR for 41-50 years = 1.47, 95% CI = 1.03-2.11), being female (adjusted OR = 2.16. 95% CI = 1.62-2.89), and being underweight (adjusted OR = 1.61, 95% CI = 1.02-2.55) were identified as risk factors for grade 3 to grade 4 ARs. Among comorbidities, only diabetes mellitus (adjusted OR = 2.36, 95% CI = 1.03-5.53) was identified as a risk factor. When stratified by the type of AR, being young and being female were risk factors for both local and systemic grade 3 to grade 4 ARs. Conclusions: Being young, female, or underweight and having diabetes mellitus were associated with an increased risk of developing grade 3 to grade 4 ARs after receiving the first dose of the ChAdOx1 nCoV-19 vaccine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lee, Lee, Lee, Moon, Moon, Chung, Yeo, Park, Won Park, Kim, Sohn, Yoon and Kim.)

Background: Rheumatic diseases are one of the most common types of chronic conditions that affect cognitive functions., Purpose: To develop and verify a hypothetical model of causal relationships between modifiable risk factors for cognitive impairment, cognitive function, self-management, and quality of life in patients with rheumatic diseases., Methods: A hypothetical model was developed on the basis of empirical evidence. The fitness of the model was verified on 210 patients with rheumatic diseases., Results: The prevalence of cognitive impairment was 49.0%. Smoking, underlying diseases, pain, and fatigue had a significant direct effect on cognitive impairment. Only cognitive impairment had a significant direct effect on self-management. Fatigue, anxiety, depression, and cognitive function had a significant direct effect on quality of life., Conclusions: The importance of proper management of symptoms and health habits should be emphasized to prevent and delay the progression of cognitive impairment and improve adherence to self-management regimens and quality of life.

Aims: Autophagy is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Whereas many studies support the importance of autophagy in the mechanisms underlying obesity-related cardiac dysfunction, the role of autophagy in cardiac lipid metabolism remains unclear. In the heart, lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates accumulation of fatty acids to the heart through intravascular triglyceride (TG) hydrolysis., Methods and Results: In both genetic and dietary models of obesity, we observed a substantial increase in cardiac LPL protein levels without any change in messenger ribonucleic acid (mRNA). This was accompanied by a dramatic down-regulation of autophagy in the heart, as revealed by reduced levels of unc-51 like kinase-1 (ULK1) protein. To further explore the relationship between cardiac LPL and autophagy, we generated cardiomyocyte-specific knockout mice for ulk1 (Myh6-cre/ulk1fl/fl), Lpl (Myh6-cre/Lplfl/fl), and mice with a combined deficiency (Myh6-cre/ulk1fl/flLplfl/fl). Similar to genetic and dietary models of obesity, Myh6-cre/ulk1fl/fl mice had a substantial increase in cardiac LPL levels. When these mice were fed a high-fat diet (HFD), they showed elevated cardiac TG levels and deterioration in heart function. However, with combined deletion of LPL and ULK1 in Myh6-cre/ulk1fl/flLplfl/fl mice, HFD feeding did not lead to alterations in levels of TG or diacylglycerol, or in cardiac function. To further elucidate the role of autophagy in cardiac lipid metabolism, we infused a peptide that enhanced autophagy (D-Tat-beclin1). This effectively lowered LPL levels at the coronary lumen by restoring autophagy in the genetic model of obesity. This decrease in cardiac luminal LPL was associated with a reduction in TG levels and recovery of cardiac function., Conclusion: These results provide clear evidence of the critical role of modulating cardiac LPL activity through autophagy-mediated proteolytic clearance as a potential novel strategy to overcome obesity-related cardiomyopathy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Aim: To assess factors associated with the higher effect of metformin on mortality in diabetic colorectal cancer (CRC) patients, since the factors related to the effectiveness of metformin have not been identified yet., Methods: Between January 2000 and December 2010, 413 patients diagnosed with both stage 3/4 CRC and diabetes mellitus were identified. Patients' demographics and clinical characteristics were analyzed. The effect of metformin on CRC-specific mortality and the interactions between metformin and each adjusted factor were evaluated., Results: Total follow-up duration was median 50 mo (range: 1-218 mo). There were 85 deaths (45.9%) and 72 CRC-specific deaths (38.9%) among 185 patients who used metformin, compared to 130 total deaths (57.0%) and 107 CRC-specific deaths (46.9%) among 228 patients who did not use metformin. In multivariate analysis, survival benefit associated with metformin administration was identified (HR = 0.985, 95%CI: 0.974-0.997, P = 0.012). Interaction test between metformin and sex after adjustment for relevant factors revealed that female CRC patients taking metformin exhibited a significantly lower CRC-specific mortality rate than male CRC patients taking metformin (HR = 0.369, 95%CI: 0.155-0.881, P = 0.025). Furthermore, subgroup analysis revealed significant differences in CRC-specific mortality between the metformin and non-metformin groups in female patients (HR = 0.501, 95%CI: 0.286-0.879, P = 0.013) but not male patients (HR = 0.848, 95%CI: 0.594-1.211, P = 0.365). There were no significant interactions between metformin and other adjusted factors on CRC-specific mortality., Conclusion: We showed a strong sex-dependent difference in the effect of metformin on CRC-specific mortality in advanced stage CRC patients with diabetes., Competing Interests: Conflict-of-interest statement: All authors declare no conflict of interest.

This Intense pulsed light (IPL) is skin therapy medical device to remove infection and lesion. The market size of IPL has increased because of increasing device users such as doctors, nurses, engineers, patients. Thus, the number of IPL approvals by Ministry of Food and Drug Safety (MFDS) has increased. However, since there are no standard and guideline for evaluation of IPL performance and safety, it is need to develop the evaluation method of IPL performance and safety for petitioners and examiners who are having difficulties in approval and review. In this study, the criteria and methods for scientific evaluation of safety and performance of IPL are proposed to support approval and review, and it is expected to enhance the international competitiveness of domestic medical device industry and patient safety. To develop the evaluation methods of IPL, first, the types and information of IPL have been collected and analyzed, and relative international and domestic standard and FDA guidance have been studied. Second, drawn test items, criteria and methods were verified at medical device testing institute. Finally, the guideline for evaluation of IPL performance and safety was reviewed through a consultative body composed of academic, industrial, institute, and government experts.

Objectives: To evaluate the feasibility and safety of the new REVO-I robotic platform by performing Fallopian tube transection and anastomosis in live porcine models., Subjects and Methods: A prospective chronic animal study was carried out in four crossbred female pigs. The primary outcome was assessment of the pigs' 2-week survival. The secondary outcomes were measurements of intra-operative variables and the complications or difficulties arising when using the REVO-I., Results: Fallopian tube anastomosis was successfully performed in four porcine models. The mean (range) operating time was 66 (46-104 min), docking time 22.25 (14-53) min and console time 18 (13-20) min. The REVO-I robotic system functioned appropriately, with no technical problems or difficulties noted during the procedures. Both the surgeon and the bedside assistants reported ease of use and better performance with subsequent procedures. All pigs were alive 2 weeks after surgery, with no peri-operative complications related to the use of the robot., Conclusions: This preclinical chronic porcine study showed that the REVO-I robotic surgical system is a feasible and safe robotic instrument that can be used by surgeons to perform skillful robotic procedures in porcine models. Our next objective will be to demonstrate its safety in humans., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

A single Au nanoparticle (NP) with a diameter of 5 nm was transferred to the end of a Si-tip through a picking process, and an Ag shell with a controlled thickness was formed on the Au core. By carrying out tip-enhanced Raman scattering (TERS) measurements on biphenyl-4-thiol (BPT) with the Au@Ag NP-tip (overall diameter of 22-60 nm), we confirm that such tips show a plasmonic local-field enhancement which is sufficient for tip-enhanced spectro-microscopy.

Purpose: CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC., Patients and Methods: CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies., Results: Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center-based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 × 10(-20)). The OR was higher for estrogen receptor (ER)-positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 × 10(-21)]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 × 10(-4)). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom., Conclusion: These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into guidelines for intensified screening and follow-up., Competing Interests: Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2016 by American Society of Clinical Oncology.)

Modulating the electric dipole field with ultrasound pulse, ultrasound current source density imaging (UCSDI) can detect current direction and form spatial 3D imaging of dipole changing in one period of treatment. As ultrasound pulse passes through the conductive media, it convolves/correlates with the inner product of the electric field of a dipole and lead field of a pair of detectors, making the shifting frequency of polarity lower than the center frequency of the ultrasound pulse. After acoustoelectric (AE) signal is shifted to base band, the AE voltage is positive at anode and negative at cathode. In the simulation, the lead fields of detectors and electric field of dipole were calculated by the finite element (FE) method; the convolution and correlation in the computation of AE signal were accelerated using 3-D fast Fourier transforms. The current direction and amplitude are encoded in the phase and amplitude of the AE signal. Based on the analysis of polarity algorithms on the simulated and in-vitro ultrasound current source density images, it is concluded that the cross-correlation method is significantly better than the autocorrelation method to extract the frequency shift for high pulse bandwidth.

Objective: Mixed results exist regarding the role of vitamin D deficiency in depression and suicidal ideation. The present study investigated the relationships among vitamin D, depressive symptoms, and suicidal ideation in a large representative of the general population of Korea., Method: The data from the fifth Korea National Health and Nutrition Examination Surveys conducted by the Division of Chronic Disease Surveillance, Korea Centers for Disease Control and Prevention, from 2010 to 2012 were investigated. A total of 15,695 subjects aged 20 and older were included in analysis. Depressive symptoms and suicidal ideation were evaluated based on self-report information. The serum 25-hydroxyvitamin D concentrations were measured by radioimmunoassay. The associations among vitamin D, depressive symptoms, and suicidal ideation were explored using multivariate logistic regression analysis adjusting for various confounding variables including sociodemographic and health-related variables., Results: Serum 25-hydroxyvitamin D concentrations were not significantly different depending on the depressive symptoms (participant with depressive symptom, n = 2085, 17.10 ng/ml; without depressive symptom, n = 13,610, 17.36 ng/ml; p = 0.142) and suicidal ideation (participant with suicidal ideation, n = 2319, 17.31 ng/ml; without suicidal ideation, n = 13,374, 17.33 ng/ml; p = 0.926). After adjustment for sociodemographic and health-related factors, this lack of relationship was held consistent in the multivariate logistic regression., Conclusions: Significant associations were not observed among vitamin D, depressive symptoms, and suicidal ideation in Korean adults. Further studies are warranted to gain a better understanding of the association among vitamin D, depressive symptoms, and suicidal ideation., (© The Author(s) 2015.)

Aim: To evaluate the long-term efficacy adefovir (ADV)-based combination therapies in entecavir (ETV)-resistant chronic hepatitis B (CHB) patients., Methods: Fifty CHB patients with genotypic resistance to ETV at 13 medical centers in South Korea were included for the analysis. All the patients received rescue therapy with the combination of ADV plus ETV (ADV/ETV, n = 23) or ADV plus lamivudine (LMV) (ADV/LMV, n = 27) for more than 12 mo. Patients were monitored at least every 3-4 mo during ADV-based combination therapy by clinical examination as well as biochemical and virological assessments. Hepatitis B virus (HBV) DNA levels were measured by real-time PCR and logarithmically transformed for analysis. Cumulative rates of virologic response (VR; HBV DNA < 20 IU/mL) were calculated using the Kaplan-Meier method, and the difference was determined by a log-rank test. Multivariate logistic regression and Cox proportional hazards models were used to identify independent risk factors significantly associated with short-term and long-term VR, respectively., Results: Baseline median HBV DNA levels were 5.53 (2.81-7.63) log10 IU/mL. The most commonly observed ETV genotypic mutation sites were rt184 and rt202. Patients were treated for a median of 27 (12-45) mo. Overall, cumulative VR rates at 6, 12, 24, and 36 mo were 26%, 36%, 45%, and 68%, respectively. Patients treated with the ADV/ETV combination showed higher cumulative VR rates (35%, 43%, 65%, and 76%, respectively) than those with the ADV/LAM combination (18%, 30%, 30%, and 62%, respectively; P = 0.048). In the multivariate analysis, low baseline HBV DNA levels (< 5.2 log10 IU/mL) and initial virologic response at 3 mo (IVR-3; HBV DNA < 3.3 log10 IU/mL after 3 mo) were independent predictive factors for VR. Patients with favorable predictors achieved cumulative VR rates up to 90% at 36 mo. During the same period, the cumulative incidence of virologic breakthrough was as low as 6% in patients with the both favorable predictors., Conclusion: If tenofovir is not available, ADV/ETV combination could be considered in ETV-resistant patients with low HBV DNA titers, and may be continued if IVR-3 is achieved.

Aim: To identify the factors that differentiate acute hepatitis B (AHB) from chronic hepatitis B with acute exacerbation (CHB-AE)., Methods: From 2004 to 2013, a total of 82 patients (male n = 52, 63.4%; female n = 30, 36.6%) with clinical features of acute hepatitis with immunoglobulin M antibodies to the hepatitis B core antigen (IgM anti-HBc) were retrospectively enrolled and divided into two groups; AHB (n = 53) and CHB-AE (n = 29). The AHB group was defined as patients without a history of hepatitis B virus (HBV) infection before the episode and with loss of hepatitis B surface antigen within 6 mo after onset of acute hepatitis. Biochemical and virological profiles and the sample/cutoff (S/CO) ratio of IgM anti-HBc were compared to determine the differential diagnostic factors., Results: The multivariate analysis demonstrated that, the S/CO ratio of IgM anti-HBc and HBV DNA levels were meaningful factors. The S/CO ratio of IgM anti-HBc was significantly higher in the AHB group, while the HBV DNA level was significantly higher in the CHB-AE group. The optimal cutoff values of IgM anti-HBc and HBV DNA levels for differentiating the two conditions were 8 S/CO ratio and 5.5 log₁₀ IU/mL, respectively. The sensitivity and specificity were 96.2% and 89.7% for the S/CO ratio of IgM anti-HBc and 81.1% and 72.4% for HBV DNA levels, respectively. The area under receiver operating characteristic curves of both the S/CO ratio of IgM anti-HBc and HBV DNA levels were not significantly different (0.933 vs 0.844, P = 0.105). When combining IgM anti-HBc and HBV DNA, the diagnostic power significantly improved compared to HBV DNA alone (P = 0.0056). The combination of these factors yielded a sensitivity and specificity of 98.1% and 86.2%, respectively., Conclusion: The combination of the S/CO ratio of IgM anti-HBc and HBV DNA levels was a useful tool for differentiating AHB from CHB-AE in patients with positive IgM anti-HBc.

Fundic gland polyps (FGPs) are currently the most common type of gastric polyps and are usually benign. However, although rare, gastric adenocarcinoma of FGP has been recently proposed as a new variant of gastric adenocarcinoma. Here we report the first case of a 49-year-old woman with focal signet ring cell carcinoma that arose from an FGP of the stomach. The tumor was completely excised by endoscopic snare polypectomy. FGPs should therefore be evaluated for malignant changes although they occur rarely, if the FGP has an erosive or irregular surface.

Twin to twin transfusion syndrome (TTTS) is caused by aberrant vascular connections between infant twins and results in high morbidity and mortality in the perinatal period. In donor infants with TTTS and symptoms of intestinal obstruction, small-bowel lesions have been reported in most cases. We report on a 33(+6) gestational wk donor infant with TTTS who had intermittent obstructive episodes, including delayed meconium passage and colonic dilatation on abdominal X-ray. The diagnosis of Hirschsprung's disease was based on a lateral pelvic film with a reversed rectosigmoid ratio. A subsequent barium colon study and rectal suction biopsy indicated a short segment aganglionosis of the colon.

Aim: To determine the etiology and prognostic factors for neonatal gastric perforation (NGP), a rare but life-threatening disease., Methods: Between 1980 and 2011, nine patients underwent surgical intervention for NGP at Seoul National University Children's Hospital. The characteristics and prognosis of the patients were retrospectively analyzed., Results: Among the nine patients, three (33.3%) were preterm babies and five (55.5%) had associated anomalies, which included diaphragmatic eventration (n = 2), congenital diaphragmatic hernia, esophageal atresia with tracheoesophageal fistula, and antral web. Three (33.3%) patients were born before 1990 and three (33.3%) had a birth weight < 2500 g. Pneumoperitoneum was found on preoperative images in six (66.7%) patients, and incidentally in the other three (33.3%) patients. Surgery was performed within 24 h after the onset of symptoms in seven (77.8%) patients. The overall mortality rate was 22.2% (2/9). The time between symptoms and surgical intervention was the only prognostic factor for survival, whereas premature birth and birth weight were not., Conclusion: Early detection and advances in neonatal intensive care may improve the prognosis of NGP.

Duodenal duplication cysts are rare congenital anomalies. Duodenal duplication should be considered in the differential diagnosis of patients who present with abdominal symptoms with cystic structures neighboring the duodenum. Here, we present an 8-year-old girl with a duodenal duplication cyst treated with partial cystectomy with mucosal stripping performed laparoscopically. Laparoscopic surgery can be considered as a treatment option for duodenal duplication cysts, especially in extraluminal locations.

Purpose: Open-label, phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer., Patients and Methods: Patients were stratified and randomly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day. Primary end point was overall survival (OS)., Results: Early trial termination occurred for futility and safety reasons. A total of 1,074 patients were randomly assigned to the study (sunitinib arm, n = 530; sorafenib arm, n = 544). For sunitinib and sorafenib, respectively, median OS was 7.9 versus 10.2 months (hazard ratio [HR], 1.30; one-sided P = .9990; two-sided P = .0014); median progression-free survival (PFS; 3.6 v 3.0 months; HR, 1.13; one-sided P = .8785; two-sided P = .2286) and time to progression (TTP; 4.1 v 3.8 months; HR, 1.13; one-sided P = .8312; two-sided P = .3082) were comparable. Median OS was similar among Asian (7.7 v 8.8 months; HR, 1.21; one-sided P = .9829) and hepatitis B-infected patients (7.6 v 8.0 months; HR, 1.10; one-sided P = .8286), but was shorter with sunitinib in hepatitis C-infected patients (9.2 v 17.6 months; HR, 1.52; one-sided P = .9835). Sunitinib was associated with more frequent and severe adverse events (AEs) than sorafenib. Common grade 3/4 AEs were thrombocytopenia (29.7%) and neutropenia (25.7%) for sunitinib; hand-foot syndrome (21.2%) for sorafenib. Discontinuations owing to AEs were similar (sunitinib, 13.3%; sorafenib, 12.7%)., Conclusion: OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib. OS was comparable in Asian and hepatitis B-infected patients. OS was superior in hepatitis C-infected patients who received sorafenib. Sunitinib-treated patients reported more frequent and severe toxicity.

Purpose: Brivanib is a dual inhibitor of vascular-endothelial growth factor and fibroblast growth factor receptors that are implicated in the pathogenesis of hepatocellular carcinoma (HCC). Our multinational, randomized, double-blind, phase III trial compared brivanib with sorafenib as first-line treatment for HCC., Patients and Methods: Advanced HCC patients who had no prior systemic therapy were randomly assigned (ratio, 1:1) to receive sorafenib 400 mg twice daily orally (n = 578) or brivanib 800 mg once daily orally (n = 577). Primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), and safety., Results: The primary end point of OS noninferiority for brivanib versus sorafenib in the per-protocol population (n = 1,150) was not met (hazard ratio [HR], 1.06; 95.8% CI, 0.93 to 1.22), based on the prespecified margin (upper CI limit for HR ≤ 1.08). Median OS was 9.9 months for sorafenib and 9.5 months for brivanib. TTP, ORR, and DCR were similar between the study arms. Most frequent grade 3/4 adverse events for sorafenib and brivanib were hyponatremia (9% and 23%, respectively), AST elevation (17% and 14%), fatigue (7% and 15%), hand-foot-skin reaction (15% and 2%), and hypertension (5% and 13%). Discontinuation as a result of adverse events was 33% for sorafenib and 43% for brivanib; rates for dose reduction were 50% and 49%, respectively., Conclusion: Our study did not meet its primary end point of OS noninferiority for brivanib versus sorafenib. However, both agents had similar antitumor activity, based on secondary efficacy end points. Brivanib had an acceptable safety profile, but was less well-tolerated than sorafenib.

Purpose: Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who cannot tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib., Patients and Methods: In all, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), and disease control rate based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and safety., Results: Median OS was 9.4 months for brivanib and 8.2 months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307). Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2% for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%)., Conclusion: In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.

Mutations of the thyroid hormone receptor-β gene (THRB) cause resistance to thyroid hormone (RTH). A mouse model of RTH harboring a homozygous thyroid hormone receptor (TR)-β mutation known as PV (Thrb(PV/PV) mouse) spontaneously develops follicular thyroid cancer (FTC). Similar to RTH patients with mutations of two alleles of the THRB gene, the Thrb(PV/PV) mouse exhibits elevated thyroid hormones accompanied by highly nonsuppressible TSH. However, the heterozygous Thrb(PV/+) mouse with mildly elevated TSH (~2-fold) does not develop FTC. The present study examined whether the mutation of a single allele of the Thrb gene is sufficient to induce FTC in Thrb(PV/+) mice under stimulation by high TSH. Thrb(PV/+) mice and wild-type siblings were treated with propylthiouracil (PTU) to elevate serum TSH. Thrb(PV/+)mice treated with PTU (Thrb(PV/+)-PTU) spontaneously developed FTC similar to human thyroid cancer, but wild-type siblings treated with PTU did not. Interestingly, approximately 33% of Thrb(PV/+)-PTU mice developed asymmetrical thyroid tumors, as is frequently observed in human thyroid cancer. Molecular analyses showed activation of the cyclin 1-cyclin-dependent kinase-4-transcription factor E2F1 pathway to increase thyroid tumor cell proliferation of Thrb(PV/+)-PTU mice. Moreover, via extranuclear signaling, the PV also activated the integrin-Src-focal adhesion kinase-AKT-metalloproteinase pathway to increase migration and invasion of tumor cells. Therefore, mutation of a single allele of the Thrb gene is sufficient to drive the TSH-simulated hyperplastic thyroid follicular cells to undergo carcinogenesis. The present study suggests that the Thrb(PV/+)-PTU mouse model potentially could be used to gain insights into the molecular basis underlying the association between thyroid cancer and RTH seen in some affected patients.

Objective: The aim of our study was to investigate the change of count and the status of cellular senescence in fetal endothelial progenitor cells (EPCs) obtained from the umbilical cord blood of women with fetal growth restriction (FGR)., Methods: Fetal EPCs were obtained from thirty five normal and thirty pregnant women with FGR. Each EPC was characterized and counted. EPC differentiation time and outgrowth endothelial cell (OEC) colony formation assay, senescence-associated β-galactosidase (SA-β-gal) activity assay, and telomerase activity assay were performed., Results: Fetal EPC counts were significantly decreased in the FGR group compared with normal controls. In the FGR group, the EPC differentiation time was prolonged, OEC colonies were much less formed, the staining intensity of SA-β-gal was relatively increased and the telomerase activity of EPCs was significantly decreased, compared with normal pregnancy (p < 0.001 for all)., Conclusions: The fetal EPCs in FGR pregnancies were decreased, functionally impaired and senescently altered.

Background: Defects in cytochrome P450c17 are uncommon forms of congenital adrenal hyperplasia caused by CYP17A1 mutations. An H373L mutation in the CYP17A1 gene has been identified in Japanese and Chinese patients. This mutation impairs 17α-hydroxylase and 17,20-lyase activity., Case: A 23-year-old Korean female (46,XX) presented with absent spontaneous puberty and hypertension. Hormonal findings were consistent with combined 17α-hydroxylase/17,20-lyase deficiency. Very high levels of progesterone and 11-deoxycorticosterone were detected, coincident with normal 17-hydroxysteroid levels. Plasma levels of dehydroepiandrosterone, androstenedione and testosterone were extremely low. Mutation analysis of the CYP17A1 gene identified a homozygous missense mutation changing His (CAC) to Leu (CTC) at codon 373. This mutation is known to completely abolish both 17α-hydroxylase and 17,20-lyase activity. The patient's nonconsanguineous parents were heterozygous for this mutation. Of note, her serum steroid levels indicated decreased, but still present, 17α-hydroxylase activity in vivo., Conclusion: We detected a homozygous H373L mutation in a patient with combined 17α-hydroxylase/17,20-lyase deficiency. Our findings demonstrate minimally preserved 17α-hydroxylase activity in vivo and contribute to our knowledge of the regional prevalence of this mutation in Northeast Asia.

Objective: To describe a cutaneous recall soft tissue injury at the site of previous extravasation of docetaxel., Case Summary: A 65-year-old white female with an invasive ductal carcinoma of the right breast was treated with carboplatin AUC 2 and docetaxel 30 mg/m(2) weekly via a peripheral vein access. During the 14th cycle, drug extravasation of docetaxel occurred in the left antecubital fossa characterized by a mild erythema without edema. A severe erythema developed in the former area of extravasation after the 15th cycle of carboplatin/docetaxel. The recall dermatitis continued to exacerbate after each course of systemic docetaxel chemotherapy and finally led to termination of this therapy., Discussion: In general, extravasation of docetaxel causes only mild local skin reactions without further necessity of intervention. For pegylated liposomal doxorubicin and paclitaxel, inflammatory recall phenomena at sites of previous drug extravasation are rare and often occur as single events following administration of the same cytotoxic drug. According to the Naranjo probability scale, the administration of docetaxel in this case probably led to the cutaneous soft tissue injury as a result of extravasation., Conclusions: Caution is needed after an episode of docetaxel extravasation. Even after a therapy interruption of several weeks, resumption of chemotherapy with docetaxel might lead to recrudescence of the inflammatory skin reaction., (© 2011 SAGE Publications.)

Background: The aim of this study was to investigate preoperative clinical and echocardiographic characteristics and N-terminal pro-B type natriuretic peptide (NT-proBNP) levels as prognostic factors for regression of the left ventricular (LV) mass after valvular surgery in patients with chronic severe mitral regurgitation (MR)., Methods: One hundred seventeen patients undergoing surgery for chronic severe MR were included. Plasma NT-proBNP measurements and echocardiography were performed preoperatively, immediately postoperatively, and at six and 12 months after surgery. Any regression of the LV mass was evaluated by echocardiography., Results: During follow-up, 90 patients (77%) were classified as an LV mass regression group (LVMR), defined as having a postoperative reduction in LV mass indexed against body surface area (LVMI). The remaining 27 (23%) patients were classified as NON-LVMR. The LVMR group was younger (p=0.029) and had significantly lower ratios of patients with hypertension (p=0.045) and diuretic use (p=0.005) than the NON-LVMR group. They also had lower levels of NT-proBNP (median: 446.4 pg/ml versus 1394.0 pg/ml, p=0.001). In multivariate analysis, higher preoperative NT-proBNP levels were independent predictors of no significant regression of the LV mass (odds ratio=1.731, 95% confidence intervals 1.052-2.844, p=0.010)., Conclusions: A lower preoperative NT-proBNP level predicted the regression of LV mass after valvular surgery in patients with chronic severe MR. This measure could be used as a biomarker for predicting the postoperative course in such patients., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Hepatocellular carcinoma (HCC) is a highly malignant tumor and extrahepatic metastasis is not rare. The most common organ of HCC metastasis is lung, followed by bone and adrenal gland. To the best of our knowledge, isolated pancreatic metastasis of HCC that developed after curative resection has not been described previously. We report a case of solitary pancreatic metastasis of HCC, which was found 28 mo after left hemihepatectomy for HCC. The lesion was successfully resected with the pancreas, and no other metastatic lesions have been found in follow-up.

The neuron-astrocyte synaptic complex is a fundamental operational unit of the nervous system. Astroglia regulate synaptic glutamate, via neurotransmitter transport by GLT1/EAAT2. Astroglial mechanisms underlying this essential neuron-glial communication are not known. We now show that presynaptic terminals regulate astroglial synaptic functions, GLT1/EAAT2, via kappa B-motif binding phosphoprotein (KBBP), the mouse homolog of human heterogeneous nuclear ribonucleoprotein K (hnRNP K), which binds the GLT1/EAAT2 promoter. Neuron-stimulated KBBP is required for GLT1/EAAT2 transcriptional activation and is responsible for astroglial alterations in neural injury. Denervation of neuron-astrocyte signaling by corticospinal tract transection, ricin-induced motor neuron death, or neurodegeneration in amyotrophic lateral sclerosis all result in reduced astroglial KBBP expression and transcriptional dysfunction of astroglial transporter expression. Presynaptic elements dynamically coordinate normal astroglial function and also provide a fundamental signaling mechanism by which altered neuronal function and injury leads to dysregulated astroglia in CNS disease.

Objectives: To identify levels of knee extensor strength that are associated with high and low risk of incident severe mobility limitation (SML) in initially well-functioning older adults., Design: Prospective cohort study., Setting: University clinic center., Participants: One thousand three hundred fifty-five men and 1,429 women (aged 73.6+/-2.85) who reported no mobility limitation., Measurements: Unilateral knee extensor isokinetic strength of participants was obtained. Participants were followed over a median of 5.90 years for the onset of SML, defined as two consecutive reports of a lot of difficulty or inability to walk one-quarter of a mile or climb 10 steps. Deciles of knee extension strength relative to body weight were evaluated to identify cutpoints most predictive of incident SML. Cutpoints were then compared with prevalence of having slow gait speed (<1.22 m/s) and mortality., Results: Two sex-specific knee extension strength cutpoints were found. High and low risk of SML corresponded to less than 1.13 newton-meters (Nm)/kg (1st decile) and more than 1.71 Nm/kg (6th decile) in men and less than 1.01 Nm/kg (3rd decile) and more than 1.34 Nm/kg (7th decile) in women, respectively. Moderate risk was defined as being between the low- and high-risk cutpoints. Individuals with knee extension strength in the high- and moderate-risk categories were more likely to have a gait speed less than 1.22 m/s (hazard ratio (HR)=7.00, 95% confidence interval (CI)=5.47-8.96 and HR=2.14 7.00, 95% CI=1.73-2.64, respectively) and had a higher risk of death (HR=1.77, 95% CI=1.41-2.23 and HR=1.51, 95% CI=1.24-1.84, respectively) than individuals in the low-risk category. Adjustment for demographic factors, health behaviors, and medical conditions did not alter these associations., Conclusion: Knee extensor strength cutpoints provide objective markers to identify initially well-functioning older adults at high and low risk of future mobility limitation.

A clip domain family of serine proteases has been identified in invertebrates as a crucial enzyme involved in diverse biological processes including immune responses and embryonic development. Although these proteins contain at least one clip domain at the N-terminal of the serine protease domain, the roles and three-dimensional structure of the clip domain are unknown. Prophenoloxidase activating factor-II (PPAF-II), a clip domain family of serine proteases, derived from the beetle Holotrichia diomphalia larvae, was overexpressed in the baculovirus system, and crystallized using the hanging-drop vapor-diffusion method. High-quality single crystals of PPAF-II were obtained in a precipitant solution containing 0.15 M ammonium sulfate, 1.25 M lithium sulfate monohydrate, and 0.1 M sodium citrate dehydrate (pH 5.5). These crystals belong to space group C2 with unit-cell parameters a=107.84, b=76.78, c=70.49 A and beta=113.93 degrees , and contain one or two molecules in the asymmetric unit. Determination of the three-dimensional structure of PPAF-II would clarify the functions of the clip domains.

Objective: To improve clinical prospects by reducing intraoperative or postoperative complications, subsequent hysterectomy is generally conducted within 48 h or 6 weeks after cervical cold-knife conization. The loop electrosurgical excision procedure (LEEP) is widely used for cervical conization. However, no study has ever been undertaken on the relation between postoperative sequelae and the time between LEEP and hysterectomy. Therefore, this study was undertaken to evaluate the correlations between postoperative sequelae and the interval between LEEP and hysterectomy., Methods: The medical records of 338 patients, who underwent type 1 extended hysterectomy after LEEP at the Department of Obstetrics and Gynecology, Yonsei University College of Medicine, were retrospectively reviewed. The subjects were divided into three groups according to time from LEEP to hysterectomy: group 1 (within 48 h, n = 210), group 2 (between 48 h and 6 weeks, n = 88), and group 3 (>6 weeks, n = 40)., Results: The three groups showed no significant differences with respect to patient characteristics (age, delivery history, body mass index, and a history of surgery). Postoperative complications such as fever, dysuria, and surgical region complications (effraction, infection, and rubefaction) were not significantly different among the three groups. Other complications, namely, ureter injury and abdominal wall hematoma, were found in one case in each group 1., Conclusion: The postoperative clinical courses were not significantly different regardless of time interval between LEEP and subsequent hysterectomy. Therefore, hysterectomies can be conducted at any time when the patient is in an appropriate condition, i.e., not precisely within 48 h or >6 weeks after LEEP.