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Background: Despite efforts to treat critically ill patients who require continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI), their mortality risk remains high. This condition may be attributable to complications of CRRT, such as arrhythmias. Here, we addressed the occurrence of ventricular tachycardia (VT) during CRRT and its relationship with patient outcomes. Methods: This study retrospectively enrolled 2,397 patients who started CRRT due to AKI from 2010 to 2020 at Seoul National University Hospital in Korea. The occurrence of VT was evaluated from the initiation of CRRT until weaning from CRRT. The odds ratios (ORs) of mortality outcomes were measured using logistic regression models after adjustment for multiple variables.Results: VT occurred in 150 patients (6.3%) after starting CRRT. Among them, 95 cases were defined as sustained VT (i.e., lasting ≥30 seconds), and the other 55 cases were defined as non-sustained VT (i.e., lasting

INTRODUCTION: Selenium is a trace mineral that is commonly included in micronutrient supplements. The effect of selenium on kidney function remains unclear. A genetically predicted micronutrient and its association with estimated glomerular filtration rate (eGFR) can be used to assess the causal estimates by Mendelian randomization (MR). METHODS: In this MR study, we instrumented 11 genetic variants associated with blood or total selenium levels from a previous genome-wide association study (GWAS). The association between genetically predicted selenium concentration and eGFR was first assessed by summary-level MR in the chronic kidney disease(CKDGen) GWAS meta-analysis summary statistics, including 567,460 European samples. Inverse-variance weighted and pleiotropy-robust MR analyses were performed, in addition to multivariable MR adjusted for the effects of type 2 diabetes mellitus. Replication analysis was performed with individual-level UK Biobank data, including 337,318 White individuals of British ancestry. RESULTS: Summary-level MR analysis indicated that a genetically predicted 1 SD increase in selenium concentration was significantly associated with lower eGFR (−1.05 [−1.28, −0.82] %). The results were similarly reproduced by pleiotropy-robust MR analysis, including MR-Egger and weighted-median methods, and consistent even in the multivariable MR adjusted for diabetes. In the UK Biobank data, genetically predicted higher selenium concentration was also significantly associated with lower eGFR (− 0.36 [−0.52, −0.20] %), and the results were similar when body mass index, waist circumference, hypertension, and diabetes mellitus covariates were adjusted (−0.33 [−0.50, −0.17] %). CONCLUSION: This MR study supports the hypothesis that higher genetically predicted body selenium is causally associated with lower eGFR.

Background: The transition of dialysis modalities from continuous renal replacement therapy (CRRT) to intermittent hemodialysis (iHD) is frequently conducted during the recovery phase of critically ill patients with acute kidney injury. Herein, we addressed the occurrence of intradialytic hypotension (IDH) after this transition, and its association with the mortality risk.Methods: A total of 541 patients with acute kidney injury who attempted to transition from CRRT to iHD at Seoul National University Hospital, Korea from 2010 to 2020 were retrospectively collected. IDH was defined as a discontinuation of dialysis because of hemodynamic instability plus a nadir systolic blood pressure

PURPOSE The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P < .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, P = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; P = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven. CONCLUSION This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481 ).

Sepsis is one of the most common causes of AKI in ICU patients, accounting for 15–20% of renal replacement therapy prescriptions. Herein, we aimed to investigate how bacterial blood culture results before CRRT correlate with mortality outcomes in patients with septic AKI requiring CRRT. The enrolled patients were divided into culture-negative, gram-positive, and gram-negative. Since the use of empirical antibiotics can affect culture-positive determination, information on antibiotic use was collected in chronological order. The primary outcome was in-hospital mortality after the initiation of CRRT. A total of 874 septic AKI patients requiring CRRT were classified into three groups: culture-negative, gram-positive cocci, and gram-negative rods. Their in-hospital mortality rates were 79.1%, 75.7%, and 61.9%, respectively (P = 0.002). In univariable Cox survival analysis performed after matching propensity scores, the gram-negative rod group was still associated with an approximately 37% reduction in mortality compared to the culture-negative group. The survival benefit of the gram-negative rod group during and after CRRT remained consistent across all subgroups, showing any P for interactions greater than 0.05. Culture-positive of gram-negative rods before CRRT initiation determine subsequent better clinical outcomes, such as lower mortality in patients undergoing CRRT due to septic AKI.

Background Interleukins (ILs), key cytokine family of inflammatory response, are closely associated with kidney function. However, the causal effect of various ILs on kidney function needs further investigation. Methods We performed two-sample summary-level mendelian randomization (MR) analysis. Genetic variants with strong association with serum IL levels were obtained from a previous genome-wide association study meta-analysis. Summary-level data for eGFR were obtained from CKDGen database. A replication analysis was performed in the independent UK Biobank data. As a main MR analysis, multiplicative random-effect inverse-variance weighed method was performed. Pleiotropy-robust MR analysis, including MR-Egger with bootstrapped error and weighed-median methods, were also implemented. Results We tested the causal estimates from nine ILs on eGFR traits. Among the results, higher genetically predicted serum IL-1ra level was significantly associated with higher eGFR values, both in the CKDGen and the UK Biobank data. In addition, the result was consistent towards eGFR decline phenotype of the outcome database. Otherwise, nonsignificant association was identified between other genetically predicted ILs and eGFR outcome. Conclusions These findings support the clinical importance of IL-1 associated pathway in relation to kidney function in the general individuals, particularly highlighting the importance of IL-1ra.

Background Hyperlactatemia occurs frequently in critically ill patients, and this pathologic condition leads to worse outcomes in several disease subsets. Herein, we addressed whether hyperlactatemia is associated with the risk of mortality in patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury. Methods A total of 1,661 patients who underwent CRRT for severe acute kidney injury were retrospectively reviewed between 2010 and 2020. The patients were categorized according to their serum lactate levels, such as high (≥ 7.6 mmol/l), moderate (2.1–7.5 mmol/l) and low (≤ 2 mmol/l), at the time of CRRT initiation. The hazard ratios (HRs) for the risk of in-hospital mortality were calculated with adjustment of multiple variables. The increase in the area under the receiver operating characteristic curve (AUROC) for the mortality risk was evaluated after adding serum lactate levels to the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score-based models. Results A total of 802 (48.3%) and 542 (32.6%) patients had moderate and high lactate levels, respectively. The moderate and high lactate groups had a higher risk of mortality than the low lactate group, with HRs of 1.64 (1.22–2.20) and 4.18 (2.99–5.85), respectively. The lactate-enhanced models had higher AUROCs than the models without lactates (0.764 vs. 0.702 for SOFA score; 0.737 vs. 0.678 for APACHE II score). Conclusions Hyperlactatemia is associated with mortality outcomes in patients undergoing CRRT for acute kidney injury. Serum lactate levels may need to be monitored in this patient subset.

Background Acidosis frequently occurs in severe acute kidney injury (AKI), and continuous renal replacement therapy (CRRT) can control this pathologic condition. Nevertheless, acidosis may be aggravated; thus, monitoring is essential after starting CRRT. Herein, we addressed the longitudinal trajectory of acidosis on CRRT and its relationship with worse outcomes. Methods The latent growth mixture model was applied to classify the trajectories of pH during the first 24 hours and those of C-reactive protein (CRP) after 24 hours on CRRT due to AKI (n = 1815). Cox proportional hazard models were used to calculate hazard ratios of all-cause mortality after adjusting multiple variables or matching their propensity scores. Results The patients could be classified into 5 clusters, including the normally maintained groups (1st cluster, pH = 7.4; and 2nd cluster, pH = 7.3), recovering group (3rd cluster with pH values from 7.2 to 7.3), aggravating group (4th cluster with pH values from 7.3 to 7.2), and ill-being group (5th cluster, pH Conclusions Initial trajectories of acidosis determine subsequent worse outcomes, such as mortality and inflammation, in patients undergoing CRRT due to AKI.

We developed highly efficient quantum dot light-emitting devices (QD-LEDs) by improving the charge balance with triple hole injection and transport layers consisted of MoO3/poly[N,N′-bis(4-butylphe...

The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified.This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25.In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5%This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481).

BackgroundThere is a notion that tobacco smoking would have weight control effect based on the appetite suppressive effect of nicotine. However, a causal effect from being an ever smoker on obesity-related traits in the general population has yet been determined.MethodsThis Mendelian randomization (MR) analysis instrumented 378 genetic variants associated with being an ever smoker which mostly initiated in adolescents or young adulthood, identified from a genome-wide association study (GWAS) meta-analysis of 1.2 million individuals. The outcome data for body mass index, waist circumference, hip circumference, and waist-to-hip ratio was collected in 337,318 white British ancestry UK Biobank participants with 40-69 ages. Replication analysis was performed for GWAS meta-analysis for body mass index including the GERA/GIANT data including 364,487 mostly European samples. Summary-level MR by inverse variance weighted method and pleiotropy-robust MR methods, including median-based and MR–Egger regression, was performed.ResultsSummary-level MR analysis indicated that genetically predicted being an ever smoker is causally linked to higher body mass index [+0.28 (0.18, 0.38) kg/m2], waist circumference [+0.88 (0.66, 1.10) cm], hip circumference [+0.40 (0.23, 0.57) cm], and waist-to-hip ratio [+0.006 (0.005, 0.007)]. The results were consistently supported by pleiotropy-robust MR analysis. In the replication analysis, genetically predicted being an ever smoker was again significantly associated with higher body mass index [+0.03 (0.01, 0.05) kg/m2].ConclusionInitiation of tobacco use may consequently lead to worse obesity-related traits of the general population in middle-to-old ages.

BackgroundAgeing traits and frailty are important health issues in modern medicine. Evidence supporting the causal effects from tobacco smoking on various ageing traits is warranted.MethodsThis Mendelian randomization (MR) analysis instrumented 377 genetic variants associated with being an ever smoker in a genome-wide significant level to test the causal estimates from tobacco smoking. The outcome data included 337,318 white British ancestry UK Biobank participants. Leukocyte telomere length, appendicular lean mass index, subjective walking pace, handgrip strength, and wristband accelerometry determined physical activity degree were collected as ageing related outcomes. Summary-level MR by inverse variance weighted method and pleiotropy-robust MR methods, including weighted median and MR–Egger, was performed.ResultsSummary-level MR analysis indicated that higher genetic predisposition for tobacco smoking was significantly associated with shorter leukocyte telomere length [2-fold prevalence increase in smoking towards standardized Z-score, -0.041 (-0.054, -0.028)], lower appendicular lean mass index [-0.007 (-0.010, -0.005)], slower walking pace [ordinal category, -0.047 (-0.054, -0.033)], and lower time spent on moderate-to-vigorous physical activity [hours per week, -0.39 (-0.56, -0.23). The causal estimates were nonsignificant towards handgrip strength phenotype [kg, 0.074 (-0.055, 0.204)]. Pleiotropy-robust MR results generally supported the main causal estimates.ConclusionGenetically predicted tobacco smoking is significantly associated with worse ageing phenotypes. Healthcare providers may continue to reduce tobacco use which may be helpful to reduce the burden related to ageing and frailty.

Introduction Whether patients with resectable colorectal liver metastases (CRLM) gain a survival benefit from perioperative chemotherapy remains controversial. The benefit of including bevacizumab in chemotherapy also remains unclear. Material and Methods Seventy-six patients with CRLM were randomly assigned to either 6 cycles of FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)/FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) with bevacizumab before and after surgery or 12 cycles after surgery. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared by the log-rank test. Results The median PFS of all patients was 37.4 months at 5.4 years follow-up, and the median overall survival (OS) was not reached. The PFS between the perioperative group and the postoperative group did not reveal a statistical difference (P = .280). The OS was significantly better in the perioperative group (hazard ratio [HR], 0.60; 95% confidence interval [CI],) 0.35-1.02; P = .049). In subgroup patients with carcinoembryonic antigens (CEA) ≥ 5 ng/mL or those with over 2 liver metastases, perioperative group had longer OS than postoperative group (CEA: HR, 0.49; 95% CI, 0.25-0.93; P = .030; number of liver metastases: HR, 0.55; 95% CI, 0.30-0.99; P = .049). The largest liver metastases size, disease-free interval, and sidedness did not affect PFS or OS. There was no difference between the 2 groups in postoperative complications with bevacizumab or adverse events during chemotherapy. Conclusions In patients with resectable CRLMs, perioperative chemotherapy had no effect on PFS, but improved OS. Patients with high CEA levels or over 2 liver metastases may benefit from perioperative chemotherapy.

Background Several studies suggest improved outcomes for patients with kidney disease who consult a nephrologist. However, it remains undetermined whether a consultation with a nephrologist is related to a survival benefit after starting continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI). Methods Data from 2,397 patients who started CRRT due to severe AKI at Seoul National University Hospital, Korea between 2010 and 2020 were retrospectively collected. The patients were divided into two groups according to whether they underwent a nephrology consultation regarding the initiation and maintenance of CRRT. The Cox proportional hazards model was used to calculate the hazard ratio (HR) of mortality during admission to the intensive care unit after adjusting for multiple variables. Results A total of 2,153 patients (89.8%) were referred to nephrologists when starting CRRT. The patients who underwent a nephrology consultation had a lower mortality rate than those who did not have a consultation (HR = 0.47 [0.40–0.56]; P < 0.001). Subsequently, patients who had nephrology consultations were divided into two groups (i.e., early and late) according to the timing of the consultation. Both patients with early and late consultation had lower mortality rates than patients without consultations, with HRs of 0.45 (0.37–0.54) and 0.51 (0.42–0.61), respectively. Conclusions Consultation with a nephrologist may contribute to a survival benefit after starting CRRT for AKI.

In this study a complete mitochondrial genome of the species, Laqueus japonicus was sequenced and analysed. The mitochondrial genome size is 14,267 bp with 20.2% A, 15.7% C, 27.1% G, and 37.0% T nucleotide distributions. This is the second complete mitochondrial genome record from the genus Laqueus and first record for the species. Genome structure and gene orientation are identical with previous record of the genus. In addition, phylogenetic relationship of L. japonicus in the subphylum Rhynchonelliformea was investigated by using protein coding genes of complete mitochondrial genome. The present study suggests that the closest species to L. japonicus is L. rubellus and they belong to the family Laqueidae.

This study used the superimposition of cone beam computed tomography (CBCT) images to evaluate three-dimensional morphologic changes in the upper airway space of skeletal class III malocclusion patients with normally positioned maxilla who had undergone mandibular setback surgery. The upper airways of 18 subjects (10 males and eight females) who underwent mandibular setback surgery were assessed using CBCT superimposition at T0 (2weeks before surgery) and T1 (1year after surgery) according to the cervical vertebrae 1 (CV1), CV2, CV3 and CV4 reference planes on CBCT. The cross-sectional area and anteroposterior width (APW) in the CV1 and CV2 planes had significantly decreased at 1year after surgery. The largest decrease was observed in the oropharynx area. However, the APW/transverse width in the CV2 plane had increased at 1year after surgery. These findings suggest that mandibular setback surgery can cause a reduction in the upper airway space; physiologic deformation of the oropharynx occurs after mandibular setback surgery.

Persistent Thebesian veins with the appearance of multiple coronary artery microfistulas are a rare finding and little is known about their physiologic and clinical features. In addition, few reports have demonstrated the perfusion status of patients with Thebesian veins. We report a 75-year-old woman referred for non-ST-elevation myocardial infarction due to prominent Thebesian veins who displayed a perfusion defect in cardiac magnetic resonance imaging.

Structured AbstractObjectives To determine differences in arch forms derived from the root apices locations between individuals with

BACKGROUND To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone-induced hiccup (DIH) in cancer patients treated with chemotherapy. MATERIALS AND METHODS Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups. RESULTS No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p

In this study, five tailed mussels were collected from the western coastal area of South Korea, and their DNA analyses were assessed by sequencing the partial mitochondrial cytochrome c oxidase subunit I (COI) gene. All DNA sequences were identified as Lingula anatina. These are the first COI record of the L. anatina from South Korea. Furthermore, the COI gene sequences of L. anatina reported from China, Japan, and Hong Kong were retrieved from GenBank, and phylogenetic relationships and genetic distances of the organisms were analyzed. Phylogenetic analysis and genetic distances suggest that the most related population with L. anatina of the present study is the Chinese population. The Japanese population diverged early from a linkage that includes Korean and Chinese populations. The Hong Kong population and one Japanese specimen examined were the most distantly related to other populations. This study provides additional data for phylogenetic study of L. anatina.

Background The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non‐small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor‐related skin adverse events (ERSEs). Materials and Methods This placebo‐controlled, double‐blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily. Results Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex‐16 after treatment were significantly different among arms (mean ± SD: −5.2 ± 8.6 for arm 1, −11.7 ± 14.2 for arm 2, and − 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm. Conclusion EGF ointment is effective for managing ERSEs. It can also improve patients’ QoL compared with placebo. Clinical trial identification number. NCT02284139 Implications for Practice Patients with non‐small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor‐related skin adverse events., Epidermal growth factor (EGFR) is an important target for antitumor therapy. This article evaluates the efficacy of EGF ointment for EGFR inhibitor‐related adverse events of the skin.

// Sung Yong Oh 1 , Aesun Shin 2 , Seong-Geun Kim 3 , Jung-Ah Hwang 4 , Seung Hyun Hong 4 , Yeon-Su Lee 4 , Hyuk-Chan Kwon 5 1 Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea 2 Department of Preventive Medicine, Seoul National University, Korea 3 Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea 4 Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Korea 5 Sillajen Inc., Busan, Korea Correspondence to: Yeon-Su Lee, email: yslee2@ncc.re.kr Hyuk-Chan Kwon, email: hckwon@sillajen.com Keywords: insulin-like growth factor, polymorphism, gastric cancer Received: January 08, 2016 Accepted: April 11, 2016 Published: April 29, 2016 ABSTRACT The insulin-like growth factor (IGF) axis plays a crucial role in proliferation, differentiation, migration, angiogenesis, and apoptosis. The present study evaluated the associations between IGF axis single-nucleotide polymorphisms (SNPs) and clinical outcomes in advanced gastric cancer (AGC) patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). A total of 190 patients undergoing FOLFOX chemotherapy for AGC were considered eligible for this study. Forty-four SNPs of 10 IGF axis genes were genotyped. Levels of serum IGF1 were measured using enzyme-linked immunoassays. SNPs of the IGF1R (rs12423791), and IGF1 (rs2162679, rs5742612, rs35767) genes were significantly associated with tumor response to FOLFOX. SNPs of rs4619 and rs17847203 were significantly associated with PFS (hazard ratio [HR] 0.575, 95% CI 0.385–0.858, P = 0.007; and HR 2.530, 95% CI 1.289–4.966, P = 0.007; respectively). SNPs of rs2872060 were significantly associated with OS—OS was shorter in patients carrying the TT variant than in those with the GG/GT genotypes (HR, 1.708, 95% CI 1.024–2.850, P = 0.040). The GT genotype of rs12847203 was also identified as an independent prognostic factor (HR 2.087, 95% CI 1.070–4.069, P = 0.031). These results suggest that IGF axis-pathway SNPs could be used as prognostic biomarkers of the outcome of FOLFOX chemotherapy in AGC patients. This information may facilitate identification of population subgroups that could benefit from IGF1R-targeted agents.

Purpose Triweekly delivery of cisplatin concurrent with a course of radiation therapy (RT) has been the standard regimen for treatment of locally advanced nasopharyngeal carcinoma (NPC) despite a high level of concern regarding treatment-related complications. We conducted a randomized phase II study to compare weekly and triweekly cisplatin delivery during RT with respect to efficacy and toxicity profiles. Material and methods Patients with locally advanced NPC (stage II–IVb) were randomly assigned to a regimen of either seven doses of cisplatin (40mg/m 2 ) given once a week or three doses of cisplatin (100mg/m 2 ) given every 3weeks concurrently during RT. Results Of 109 eligible patients, 53 were assigned to the weekly regimen and 56 to the triweekly regimen. The two groups were comparable with respect to demographic and clinical characteristics. There were no significant differences in mean RT dose (68.3Gy vs. 67.3Gy, p =0.559) and mean cisplatin dose (248.9mg/m 2 vs. 256.6mg/m 2 , p =0.433) between the two regimens. The primary endpoint was 3-year progression-free survival, which was not different between the regimens (64.9% vs. 63.8%, p =0.074). Overall, the occurrence of grade 3–4 toxicities was similar between the two arms (47.2% vs. 39.3%, p =0.443). Quality of life (QoL) related to functional outcomes 3weeks after treatment completion was better for the weekly regimen. Conclusions Although no definitive conclusions can be made, a once-weekly cisplatin regimen appears to be associated with improved QoL and is not inferior to the standard triweekly regimen with respect to efficacy and toxicity profiles.

Pexa-Vec (JX-594) is a specific cancer-targeted oncolytic and immunotherapeutic vaccinia virus. The purpose of this study was to develop methods to maximize the stability of Pexa-Vec. In short-term instability testing, viral activity was rapidly decreased both at 4°C and at room temperature (RT), but it was completely restored after sonication followed by vortex. Long-term stability testing of Pexa-Vec in the following liquid formulations was performed: (A) 30 mM Tris/pH 7.6, (B) 30 mM Tris/pH 8.6,(C) 30 mM Tris/pH 7.6, 150 mM NaCl, 15% sucrose, (D) 30 mM Tris/pH 7.6, 15% sucrose, and (E) 30 mM Tris/pH 8.6, 15% sucrose. Viral activity decreased less than 2 log10 at 4°C, and RT was observed in 3 days in B, while viral activity was not decreased even after 4–8 weeks at 4°C and at 1 week in RT in A, suggesting that neutral pH may be essential to maintain virus stability. The addition of 15% sucrose into A (D) significantly increased viral stability at -20°C, 4°C, or RT, and it was also observed at pH 8.6 (E). The addition of 150 mM NaCl into D (C) significantly increased viral stability in addition to the sucrose effect at 4°C or RT. Accordingly, the viral activity in formulation C was maintained for 1.5 years at 4°C, and for 1-2 weeks in RT. In conclusion, we propose that formulation C can provide the most adequate condition for the proper storage of vaccinia oncolytic virus.

The objectives of this study identify the factors that affect the quality of MTS services, to determine the effects of these service quality factors on customer's satisfaction and customer's loyalty. The results are as follows: First, The Four factors, i.e., tangibles, reliability, responsiveness, and assurance, represent statistically marginal significance in explaining the relationship between MTS service quality factors and customer's satisfaction. Second, The Five factors, i.e., rapidness, tangibles, responsiveness, empathy, and assurance represent statistically marginal significance in explaining the relationship between MTS service quality factors and customer's loyalty. Third, There are some differences in assurance/period of utilization, empathy/period of utilization in using MTS services according to social statistics. This article provides the paradigm of new convergence on IT and finance. Key Words : MTS, Service Quality, Customer Satisfaction, Customer Loyalty, Convergence of IT and Online Security Trading

We examined the effectiveness of using different calcium salts for bioconsolidation. Four calcium salts were chosen based on their applicability and solubility. Initial experiments demonstrated that the addition of any calcium salt had a negative effect on the urease activity of S. pasteurii. Microscopic examinations elucidated the morphological and structural differences of the calcium carbonate (CaCO3) crystals induced. Calcite and vaterite are the prominent forms of CaCO3 detected according to X-ray diffraction (XRD) analysis. Bioconsolidated sand samples were able to significantly resist water flow through a column compared to the non-treated samples. Also, in a tightness test, the differences in the ability to retain water within columns were observed among the samples tested. Moreover, despite the differences, the calcium salts tested still bound the sand together to form blocks. Our results further explain the influence of multiple factors in crystal formation and sand bioconsolidation effectiveness.

// Nam Hee Lee 1, 2 , Mikyung Kim 1 , Sung Yong Oh 3 , Seong-Geun Kim 4 , Hyuk-Chan Kwon 1 , Tae-Ho Hwang 5, 6 1 SillaJen, Inc., Busan, Korea 2 Department of Physiology, Pusan National University, School of Medicine, Yangsan, Korea 3 Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea 4 Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea 5 Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Korea 6 Gene and Cell Therapy Research Center for Vessel-associated Diseases, School of Medicine, Pusan National University, Yangsan, Korea Correspondence to: Tae-Ho Hwang, email: thhwang@pusan.ac.kr Hyuk-Chan Kwon, email: hckwon@sillajen.com Keywords: oncolytic virus, gene expression profiling, hematologic malignancy Received: August 20, 2016 Accepted: November 04, 2016 Published: November 25, 2016 ABSTRACT Pexa-Vec (pexastimogene devacirpvec; JX-594) has emerged as an attractive tool in oncolytic virotherapy. Pexa-Vec demonstrates oncolytic and immunotherapeutic mechanisms of action. But the determinants of resistance to Pexa-Vec are mostly unknown. We treated hemoatologic malignant cells with Pexa-Vec and examined the gene-expression pattern of sensitive and resistant cells. Human myeloid malignant cell lines (RPMI-8226, IM-9, K562, THP-1) and lymphoid cancer cell lines (MOLT4, CCRF-CEM, Ramos, U937) were treated with Pexa-Vec. Pexa-Vec was cytotoxic on myeloid cell lines in a dose-dependent manner, and fluorescent imaging and qPCR revealed that Pexa-Vec expression was low in RAMOS than IM-9 after 24 hrs and 48 hrs of infection. Gene expression profiles between two groups were analyzed by microarray. Genes with at least 2-fold increase or decrease in their expression were identified. A total of 660 genes were up-regulated and 776 genes were down-regulated in lymphoid cancer cell lines. The up- and down-regulated genes were categorized into 319 functional gene clusters. We identified the top 10 up-regulated genes in lymphoid cells. Among them three human genes (LEF1, STAMBPL1, and SLFN11) strongly correlated with viral replication. Up-regulation of PVRIG, LPP, CECR1, Arhgef6, IRX3, IGFBP2, CD1d were related to resistant to Pexa-Vec. In conclusion, lymphoid malignant cells are resistant to Pexa-Vec and displayed up-regulated genes associated with resistance to oncolytic viral therapy. These data provide potential targets to overcome resistance, and suggest that molecular assays may be useful in selecting patients for further clinical trials with Pexa-Vec.

Background This study was conducted to propose the optimal duration of fluoropyrimidine-based adjuvant chemotherapy consisting of fluoropyrimidine derivatives alone or combined with intravenous platinum for stage II or III gastric cancer (GC). Methods We analyzed retrospectively the data from 2219 patients with histologically confirmed adenocarcinoma in the stomach, who underwent a curative gastrectomy with lymphadenectomy from 2005 to 2012. Five-year overall survival (OS) and 3-year relapse-free survival (RFS) were analyzed according to the duration of fluoropyrimidine-based adjuvant chemotherapy. Results Data from 617 patients with stage II or III GC were analyzable; 187 patients (30.3 %) were treated with surgery alone, while 430 patients (69.7 %) were treated with postoperative adjuvant chemotherapy. The duration of adjuvant chemotherapy was less than 6 months [group 1] in 147 patients (34.2 %), 6 months to less than 12 months [group 2] in 94 patients (21.9 %), 1 year to less than 2 years [group 3] in 139 patients (32.3 %), and over 2 years [group 4] in 50 patients (11.6 %). The 5-year OS in groups 1, 2, 3, and 4 was 75.7, 87, 90.3, and 93.4 %, respectively, while 3-year RFS was 52.5, 58.8, 81.4, and 94.0 %, respectively. Conclusions In this retrospective study, we did not demonstrate any significant improvement in OS and RFS by longer periods of fluoropyrimidine-based adjuvant chemotherapy in stage II or III GCs. Further prospective randomized studies are needed.

In this study a complete mitochondrial genome of the species, Laqueus japonicus was sequenced and analysed. The mitochondrial genome size is 14,267 bp with 20.2% A, 15.7% C, 27.1% G, and 37.0% T nucleotide distributions. This is the second complete mitochondrial genome record from the genus Laqueus and first record for the species. Genome structure and gene orientation are identical with previous record of the genus. In addition, phylogenetic relationship of L. japonicus in the subphylum Rhynchonelliformea was investigated by using protein coding genes of complete mitochondrial genome. The present study suggests that the closest species to L. japonicus is L. rubellus and they belong to the family Laqueidae.

In this study, complete mitochondrial genome of the Lingula anatina (Lamark, 1801) from Korea has been sequenced and analysed, and compared with previous complete mitochondrial genome record from Japan. The mitogenome is 25,790 bp and composed of 13 protein-coding genes, two ribosomal RNA and 34 tRNA. In comparison with previous record, there are dramatically changes in structure between two records. Additionally, phylogenetic tree of L. anatina in Brachiopoda reconstructed due to 12 protein-coding genes of mitochondrial genome. The results showed that the Korean L. anatina positioned in Brachiopoda and the closest species is the L. anatina from the Japan. This study provides the second complete mitochondrial genome for the species.

Microbicides are used to eliminate pathogenic bacteria, but they can also eliminate beneficial and normal bacteria. This study provides antimicrobial information of mandelic acid (MA) prior to its widespread use. The MA susceptibilities of Lactobacillus sp. and pathogens were determined by dilution method based on NCCLS protocol. The concentration of MA at 5.0 mg/mL inhibited 90% of the Lactobacillus sp., whereas a 1.25 mg/mL concentration inhibited the following pathogenic bacteria strains: Listeria monocytogenes KCTC3710, Yersinia enterocolitica ATCC23715, and Shigella sonnei ATCC9290. The minimal inhibitory concentration (MIC) for Escherichia coli O157:H7, Salmonella enteritidis KCTC12400, Salmonella gallinarum ATCC9148, Salmonella typhimurium ATCC29631, and Staphylococcus aureus KCCM40881 was at 2.5 mg/mL. These pathogens were also inhibited by addition of 1.0 M NaCl in 2 mg/mL MA solution (pH 5.0), while lactobacilli were not affected. These results indicate that MA can prevent disease and food poisoning when applied as a disinfectant in food industry, hospitals, and public places.

3528Background: Whether patients with resectable colorectal cancer liver metastases (CRLM) gain a survival benefit or not from neoadjuvant chemotherapy remains controversial. The addition of bevaci...

10054Background: The efficacy of the EGFR inhibitors has been demonstrated in non-small cell lung cancer (NSCLC), pancreatic cancer (PC) and colorectal cancer (CRC). Dermatological reactions can ca...

671 Background: Pexa-Vec is a vaccinia virus engineered to express granulocyte-macrophage colony stimulating factor (GM-CSF), thereby stimulating anti-tumor immunity, direct oncolysis, and tumor vascular disruption. ( Nat Rev Cancer 2009). Pexa-Vec was shown to replicate in metastatic tumors following intratumoral (IT) or intravenous (IV) administration ( Lancet Oncol 2008; Nature 2011). Methods: RCC patients failing at least 1 prior VEGF/R-targeted therapy received five weekly IV Pexa-Vec infusions. Starting at Week 6, patients with disease control or otherwise clinically benefitting from treatment could continue to receive IV infusions every 3 weeks. The primary study objective was radiographic response based on modified Response Evaluation Criteria (RECIST) 1.0. Secondary objectives included disease control rate, progression free survival and safety. Results: All seventeen patients enrolled received the initial 5 weekly Pexa-Vec infusions. Twelve patients received at least one additional infusion (median Pexa-Vec infusions = 8; range 5-12). The treatment regimen was well-tolerated. Transient influenza-like illness (100%), asthenia (47%), anemia (29%) and nausea (29%) were the most common adverse events. All patients were evaluable radiographically at Week 6. The RECIST disease control rate was 76% at Week 6 including 1 complete response. Conclusions: Pexa-Vec was well-tolerated and associated with one complete RECIST response and 76% disease control at Week 6 in patients with advanced RCC. Further trials of Pexa-Vec in RCC patients are warranted.