Cardiovascular risk associated with allopurinol or benzbromarone treatment in patients with gout.

Background: In previous studies, cardiovascular (CV) risk was increased in patients with gout. The effects of uric acid-lowering therapy on CV risk in gout patients have been investigated in numerous studies; however, allopurinol and benzbromarone have rarely been compared. Objectives: To compare CV risk based on allopurinol and benzbromarone treatment in Korean gout patients. Design: A nationwide population-based retrospective cohort study. Methods: We used South Korea database of the Health Insurance Review and Assessment (HIRA) service to identify gout patients ⩾18 years of age who newly started allopurinol or benzbromarone between 2009 and 2015. The primary outcome of the study was the occurrence of a composite CV endpoint, which included coronary revascularization, hospitalization due to myocardial infarction, ischemic stroke, and transient ischemic attack. Cox proportional hazard regression analysis and Kaplan-Meier curves were used for analysis. Results: The study included 257,097 allopurinol initiators and 7868 benzbromarone initiators. Compared with allopurinol initiators, the adjusted hazard ratio (aHR) of the composite CV endpoint of benzbromarone initiators was 1.01 [95% confidence interval (CI): 0.83-1.21], which was not significantly different. The results did not change even when 1:3 propensity score matching was performed for baseline characteristics. In subgroup analysis of high-risk patients with CV disease, significant difference was not observed between allopurinol and benzbromarone initiators. Conclusion: In this study, significant difference was not found in CV risk between allopurinol and benzbromarone initiators. In the high-CV-risk group, the incidence of CV events did not differ between allopurinol and benzbromarone initiators.

Ductal carcinoma in situ: a risk prediction model for the underestimation of invasive breast cancer.

Patients with a biopsy diagnosis of ductal carcinoma in situ (DCIS) may be diagnosed with invasive breast cancer after excision. We evaluated the preoperative clinical and imaging predictors of DCIS that were associated with an upgrade to invasive carcinoma on final pathology and also compared the diagnostic performance of various statistical models. We reviewed the medical records; including mammography, ultrasound (US), and magnetic resonance imaging (MRI) findings; of 644 patients who were preoperatively diagnosed with DCIS and who underwent surgery between January 2012 and September 2018. Logistic regression and three machine learning methods were applied to predict DCIS underestimation. Among 644 DCIS biopsies, 161 (25%) underestimated invasive breast cancers. In multivariable analysis, suspicious axillary lymph nodes (LNs) on US (odds ratio [OR], 12.16; 95% confidence interval [CI], 4.94-29.95; P < 0.001) and high nuclear grade (OR, 1.90; 95% CI, 1.24-2.91; P = 0.003) were associated with underestimation. Cases with biopsy performed using vacuum-assisted biopsy (VAB) (OR, 0.42; 95% CI, 0.27-0.65; P < 0.001) and lesion size <2 cm on mammography (OR, 0.45; 95% CI, 0.22-0.90; P = 0.021) and MRI (OR, 0.29; 95% CI, 0.09-0.94; P = 0.037) were less likely to be upgraded. No significant differences in performance were observed between logistic regression and machine learning models. Our results suggest that biopsy device, high nuclear grade, presence of suspicious axillary LN on US, and lesion size on mammography or MRI were independent predictors of DCIS underestimation.

Selenium Nanoparticles as Candidates for Antibacterial Substitutes and Supplements against Multidrug-Resistant Bacteria.

In recent years, multidrug-resistant (MDR) bacteria have increased rapidly, representing a major threat to human health. This problem has created an urgent need to identify alternatives for the treatment of MDR bacteria. The aim of this study was to identify the antibacterial activity of selenium nanoparticles (SeNPs) and selenium nanowires (SeNWs) against MDR bacteria and assess the potential synergistic effects when combined with a conventional antibiotic (linezolid). SeNPs and SeNWs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), zeta potential, and UV-visible analysis. The antibacterial effects of SeNPs and SeNWs were confirmed by the macro-dilution minimum inhibitory concentration (MIC) test. SeNPs showed MIC values against methicillin-sensitive S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-resistant S. aureus (VRSA), and vancomycin-resistant enterococci (VRE) at concentrations of 20, 80, 320, and >320 µg/mL, respectively. On the other hand, SeNWs showed a MIC value of >320 µg/mL against all tested bacteria. Therefore, MSSA, MRSA, and VRSA were selected for the bacteria to be tested, and SeNPs were selected as the antimicrobial agent for the following experiments. In the time-kill assay, SeNPs at a concentration of 4X MIC (80 and 320 µg/mL) showed bactericidal effects against MSSA and MRSA, respectively. At a concentration of 2X MIC (40 and 160 µg/mL), SeNPs showed bacteriostatic effects against MSSA and bactericidal effects against MRSA, respectively. In the synergy test, SeNPs showed a synergistic effect with linezolid (LZD) through protein degradation against MSSA and MRSA. In conclusion, these results suggest that SeNPs can be candidates for antibacterial substitutes and supplements against MDR bacteria for topical use, such as dressings. However, for use in clinical situations, additional experiments such as toxicity and synergistic mechanism tests of SeNPs are needed.

The effect of norepinephrine on common carotid artery blood flow in septic shock patients.

This study was designed to evaluate the hemodynamic effect of norepinephrine (NE) on the peak systolic velocity (PSV), diameter, and blood flow of the common carotid artery (CCA) using the point-of-care ultrasound (POCUS) in patients with septic shock. The study involved patients above 18 years old with septic shock. Arterial monitoring, carotid ultrasonography, and transthoracic echocardiography were performed before NE administration (T0). When the mean arterial pressure exceeded 65 mmHg after NE administration (T1), the measurement was repeated. Twenty-four patients (median age 67 [interquartile range: 54-77] years; 42% female) with septic shock were examined in this study. Before (T0) and after (T1) NE administration, the PSV (mean, standard deviation [SD]) changed from 85.3 (21.1) cm/s to 83.5 (23.5) cm/s (p = 0.417); this change was not significant. However, the diameter and blood flow of the CCA increased significantly from 0.6 (0.09) cm and 0.75 (0.27) L/min to 0.66 (0.09) cm and 0.85 (0.27) L/min, respectively (p < 0.001). The diameter of the left ventricular outflow tract (LVOT) remained unchanged, but the velocity time integral of the LVOT increased significantly from 21.7 (4.39) cm to 23.6 (5.14) cm. There was no significant correlation between changes in blood flow of the CCA and changes in cardiac output (coefficient -0.365, p = 0.079). In conclusion, NE increased the diameter and blood flow of the CCA significantly, without changing the PSV in patients with septic shock.

Grapefruit Seed Extract as a Natural Derived Antibacterial Substance against Multidrug-Resistant Bacteria.

Multidrug-resistant (MDR) bacteria are increasing due to the abuse and misuse of antibiotics, and nosocomial infections by MDR bacteria are also increasing. The aim of this study was to identify new substances that can target MDR bacteria among 12 plant extracts that are known to have antibacterial effects. The experiments were performed by the disk diffusion test and microdilution minimum inhibitory concentration (MIC) test, as described by the Clinical and Laboratory Standards Institute (CLSI). By screening against methicillin-sensitive Staphylococcus aureus (MSSA), grapefruit seed extract (GSE) was selected from 12 plant extracts for subsequent experiments. GSE showed antibacterial effects against methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) in the disk diffusion test. Even at the lowest concentration, GSE showed antibacterial activity in the microdilution MIC test. As a result, we can conclude that GSE is a naturally derived antibacterial substance that exhibits a favorable antibacterial effect even at a very low concentration, so it is a good candidate for a natural substance that can be used to prevent or reduce nosocomial infections as coating for materials used in medical contexts or by mixing a small amount with other materials.

iCSDB: an integrated database of CRISPR screens.

High-throughput screening based on CRISPR-Cas9 libraries has become an attractive and powerful technique to identify target genes for functional studies. However, accessibility of public data is limited due to the lack of user-friendly utilities and up-to-date resources covering experiments from third parties. Here, we describe iCSDB, an integrated database of CRISPR screening experiments using human cell lines. We compiled two major sources of CRISPR-Cas9 screening: the DepMap portal and BioGRID ORCS. DepMap portal itself is an integrated database that includes three large-scale projects of CRISPR screening. We additionally aggregated CRISPR screens from BioGRID ORCS that is a collection of screening results from PubMed articles. Currently, iCSDB contains 1375 genome-wide screens across 976 human cell lines, covering 28 tissues and 70 cancer types. Importantly, the batch effects from different CRISPR libraries were removed and the screening scores were converted into a single metric to estimate the knockout efficiency. Clinical and molecular information were also integrated to help users to select cell lines of interest readily. Furthermore, we have implemented various interactive tools and viewers to facilitate users to choose, examine and compare the screen results both at the gene and guide RNA levels. iCSDB is available at https://www.kobic.re.kr/icsdb/.

Effect of baseline sarcopenia on adjuvant treatment for D2 dissected gastric cancer: Analysis of the ARTIST phase III trial.

BACKGROUND AND PURPOSE: This study evaluated the clinical significance of preoperative sarcopenia according to adjuvant concurrent chemo-radiotherapy (XP-RT) or chemotherapy alone (XP) in the D2 dissected gastric cancer patient cohort of the ARTIST trial. MATERIALS AND METHODS: Skeletal muscles at the L3 vertebra level from preoperative computed tomography images among the ARTIST trial participants were measured using validated in-house software. Skeletal muscle index (SMI) was defined as the measured skeletal muscle area divided by the square of the height, and sarcopenia was defined according to the Korean-specific cutoff, i.e. L3 SMI ≤ 49 cm2/m2 for men and ≤31 cm2/m2 for women. RESULTS: Among the 440 patients in whom we were able to evaluate L3 SMI, 75 (17.0%) met the definition for preoperative sarcopenia. No differences in treatment-related toxicities or treatment compliance were observed according to the presence of preoperative sarcopenia in either treatment arm. In the subgroup of patients without preoperative sarcopenia, recurrence was significantly lower in the XP-RT arm than that in the XP arm (p = 0.02). Recurrence-free survival (RFS) was also significantly higher in the XP-RT arm (p = 0.02, hazard ratio 0.633, 95% confidence interval 0.433-0.926) in this subgroup. In the multivariate analysis, and after adjusting for significant prognostic factors, the superior outcome of XP-RT arm regarding RFS was maintained in the subgroup of the patients without preoperative sarcopenia. CONCLUSIONS: Superior clinical outcomes of adjuvant XP-RT over XP were only observed in patients without preoperative sarcopenia.

Effect of Perfluorobutane Microbubbles on Radiofrequency Ablation for Hepatocellular Carcinoma: Suppression of Steam Popping and Its Clinical Implication.

OBJECTIVE: To evaluate the effect of perfluorobutane microbubbles (Sonazoid®, GE Healthcare) on steam popping during radiofrequency (RF) ablation for treating hepatocellular carcinoma (HCC), and to assess whether popping affects treatment outcomes. MATERIALS AND METHODS: The institutional review board approved this retrospective study, which included 90 consecutive patients with single HCC, who received percutaneous RF ablation as the first-line treatment. The patients were divided into two groups, based on the presence or absence of the popping phenomenon, which was defined as an audible sound with a simultaneous sudden explosion within the ablation zone as detected via ultrasonography during the procedure. The factors contributing to the popping phenomenon were identified using multivariable logistic regression analysis. Local tumor progression (LTP) and disease-free survival (DFS) were assessed using the Kaplan-Meier method with the log-rank test for performing comparisons between the two groups. RESULTS: The overall incidence of the popping phenomenon was 25.8% (24/93). Sonazoid® was used in 1 patient (4.2%) in the popping group (n = 24), while it was used in 15 patients (21.7%) in the non-popping group (n = 69). Multivariable analysis revealed that the use of Sonazoid® was the only significant factor for absence of the popping phenomenon (odds ratio = 0.10, p = 0.048). There were no significant differences in cumulative LTP and DFS between the two groups (p = 0.479 and p = 0.424, respectively). CONCLUSION: The use of Sonazoid® has a suppressive effect on the popping phenomenon during RF ablation in patients with HCC. However, the presence of the popping phenomenon may not affect clinical outcomes.

Outcomes of Radiotherapy for Mesenchymal and Non-Mesenchymal Subtypes of Gastric Cancer.

Background: The purpose of this study was to evaluate the clinical outcomes following postoperative chemotherapy (XP) versus chemoradiotherapy (XP-RT) according to mesenchymal subtype based on RNA sequencing in gastric cancer (GC) in a cohort of the Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. Methods: Of the 458 patients enrolled in the ARTIST trial, formalin-fixed, paraffin-embedded (FFPE) specimens were available from 106 (23.1%) patients for RNA analysis. The mesenchymal subtype was classified according to a previously reported 71-gene MSS/EMT signature using the NanoString assay. Results: Of the 106 patients analyzed (50 in XP arm, 56 in XP-RT arm), 36 (34.0%) patients were categorized as mesenchymal subtype by NanoString assay. Recurrence-free survival (RFS, p = 0.009, hazard ratio (HR) = 2.11, 95% confidence interval (CI): 1.21-3.70) and overall survival (OS, p = 0.003, HR = 2.28, 95% CI: 1.31-3.96) were significantly lower in the mesenchymal subtype than in the non-mesenchymal subtype. In terms of post-operative radiotherapy (RT), mesenchymal subtype was not an independent variable to predict RFS or OS regardless to the assigned arm (XP with or without RT) in this patient cohort. However, there was a trend in the adjuvant XP arm, which showed higher OS than the XP-RT arm for the mesenchymal subtype and lower OS than the XP-RT arm for the non-mesenchymal subtype. Conclusions: We could not determine any significant differences between the mesenchymal and non-mesenchymal subtypes with respect to the effects of adjuvant XP with or without RT in gastric cancer following curative surgery.

C-MAC Video Laryngoscope versus Conventional Direct Laryngoscopy for Endotracheal Intubation During Cardiopulmonary Resuscitation.

Background and objectives: To compare the first pass success (FPS) rate of the C-MAC video laryngoscope (C-MAC) and conventional Macintosh-type direct laryngoscopy (DL) during cardiopulmonary resuscitation (CPR) in the emergency department (ED). Materials and Methods: This study was a single-center, retrospective study conducted from April 2014 to July 2018. Patients were categorized into either the C-MAC or DL group, according to the device used on the first endotracheal intubation (ETI) attempt. The primary outcome was the FPS rate. A multiple logistic regression model was developed to identify factors related to the FPS. Results: A total of 573 ETIs were performed. Of the eligible cases, 263 and 310 patients were assigned to the C-MAC and DL group, respectively. The overall FPS rate was 75% (n = 431/573). The FPS rate was higher in the C-MAC group than in the DL group, but there was no statistically significant difference (total n = 431, 79% compared to 72%, p = 0.075). In the multiple logistic regression analysis, the C-MAC use had higher FPS rate (adjusted odds ratio: 1.80; 95% CI, 1.17-2.77; p = 0.007) than that of the DL use. Conclusions: The C-MAC use on the first ETI attempt during cardiopulmonary resuscitation in the emergency department had a higher FPS rate than that of the DL use.

Tumor Heterogeneity Index to Detect Human Epidermal Growth Factor Receptor 2 Amplification by Next-Generation Sequencing: A Direct Comparison Study with Immunohistochemistry.

Intratumoral heterogeneity of human epidermal growth factor receptor 2 (HER2) is common in gastric cancer (GC). However, a direct comparison between the results of HER2 immunohistochemistry (IHC) and next-generation sequencing (NGS)-based cancer panel tests has not been explored in GC. We aimed to determine optimal thresholds of HER2 overexpression to be detected by NGS with the data of 168 metastatic GC cases with known expression levels of HER2 by IHC and the copy number alteration of ERBB2 obtained by NGS test by applying tumor heterogeneity index (THI) and receiver operating characteristic curve. GC tissues were obtained via biopsy (N = 103) and gastrectomy (N = 65). HER2 3+ by IHC was observed in 27 cases (16%), and 14 of 27 HER2 IHC 3+ cases (52%) showed intratumoral heterogeneity (<90% of tumor cells are HER2 3+). Of 27 HER2 3+ cases, 19 (70%) were detected by NGS. All eight cases with discrepant IHC and NGS results harbored intratumoral heterogeneity. The receiver operating characteristic curve analysis showed that the optimal value of THI to be detected by NGS was a score of 72 for biopsy specimens and 120 for resection specimens. In conclusion, intratumoral heterogeneity of HER2 expression is observed in 52% of metastatic GC cases. NGS laboratories should be aware that accuracy of ERBB2 copy number alteration detection by NGS is influenced by the THI.