Comparison of Four Diagnostic Guidelines for Hepatocellular Carcinoma Using Gadoxetic Acid-enhanced Liver MRI.

Background Noninvasive diagnostic guidelines for hepatocellular carcinoma (HCC) vary across different global geographic areas, especially regarding criteria about gadoxetic acid-enhanced MRI. Purpose To compare the diagnostic performance of four different international HCC diagnosis guidelines and readers' judgment in diagnosing HCC using gadoxetic acid-enhanced MRI in patients at high risk for HCC. Materials and Methods This retrospective study included patients who had not undergone treatment, were at risk for HCC, and who underwent gadoxetic acid-enhanced MRI from January 2015 to June 2018 from 11 tertiary hospitals in South Korea. Four radiologists independently reviewed focal liver lesions (FLLs) according to four guidelines: American Association for the Study of Liver Diseases (AASLD)/Liver Imaging Reporting and Data System (LI-RADS), Korean Liver Cancer Association-National Cancer Center (KLCA-NCC), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). Reader judgment (HCC or not HCC) was also recorded. Malignant FLLs were confirmed at pathology, and histologic and clinical follow-up data were used for benign FLLs. The guidelines' diagnostic performance was compared using generalized estimating equations. Additionally, the diagnostic odds ratio was assessed. Results A total of 2445 FLLs (median size, 27.4 mm) were analyzed in 2237 patients (mean age, 59 years ± 11 [SD]; 1666 male patients); 69.3% (1694 of 2445) were HCCs. KLCA-NCC showed the highest accuracy (80.0%; 95% CI: 78.7, 81.2; P = .001), with high sensitivity in Eastern guidelines (APASL, 89.1% [95% CI: 87.8, 90.3]; KLCA-NCC, 78.2% [95% CI: 76.6, 79.7]) and high specificity in Western guidelines (AASLD/LI-RADS, 89.6% [95% CI: 87.8, 91.2]; EASL, 88.1% [95% CI: 86.2, 89.9]) (P = .001). The diagnostic odds ratios were 20.7 (95% CI: 17.0, 25.3) for AASLD/LI-RADS, 18.9 (95% CI: 15.8, 22.6) for KLCA-NCC, 16.8 (95% CI: 13.8, 20.4) for EASL, and 8.9 (95% CI: 7.4, 10.7) for APASL. The readers' judgment demonstrated higher accuracy than that of the guidelines (accuracy, 86.0%; 95% CI: 84.9, 86.9; P = .001). Conclusion Among four different international HCC diagnosis guidelines, Eastern guidelines demonstrated higher sensitivity, whereas Western guidelines displayed higher specificity. KLCA-NCC achieved the highest accuracy, and AASLD/LI-RADS exhibited the highest diagnostic odds ratio. © RSNA, 2024 Supplemental material is available for this article.

8-Iso-prostaglandin F2α as a biomarker of type 2 low airway inflammation and remodeling in adult asthma.

BACKGROUND: Although 8-iso-prostaglandin F2a has been proposed as a potential biomarker for oxidative stress in airway diseases, its specific role in asthma remains poorly understood. OBJECTIVE: To evaluate the diagnostic potential of 8-iso-prostaglandin F2a in assessing airway inflammation, airway remodeling, airway hyperresponsiveness, and oxidative stress in asthma. METHODS: Blood and urine concentrations of 8-iso-prostaglandin F2a were quantified using liquid chromatography-tandem mass spectrometry in 128 adults with asthma who had maintained antiasthma medications. Their correlations with clinical data, sputum cell counts, lung function parameters, and serum markers of epithelial/neutrophil activity and airway remodeling were then analyzed. RESULTS: The urinary 8-iso-prostaglandin F2a concentrations were significantly higher in patients with noneosinophilic asthma than in those with eosinophilic asthma (P < .05). The area under the curve was 0.678, indicating moderate diagnostic accuracy for noneosinophilic asthma. There were significant correlations with neutrophilic inflammation markers and airway remodeling markers (all P < .05). Negative correlations were observed with forced expiratory volume in 1 second (%), forced expiratory volume in 1 second/forced vital capacity, forced expiratory flow at 25% to 75% of forced vital capacity, and serum club cell protein 16 levels (all P < .05). High 8-iso-prostaglandin F2a concentrations were also noted in obese and smoking subgroups (all P < .05). However, the serum 8-iso-prostaglandin F2a concentrations were not correlated with these asthma-related parameters. CONCLUSION: Urinary 8-iso-prostaglandin F2a concentrations are a potential biomarker for phenotyping severe asthma, particularly noneosinophilic asthma, offering oxidative stress-induced epithelial inflammation/remodeling as an additional target in asthma management.

Utility of abbreviated MRI in the post-treatment evaluation of rectal cancer.

BACKGROUND: Post-treatment evaluation of patients with rectal cancer (RC) using magnetic resonance imaging (MRI) burdens medical resources, necessitating an exploration of abbreviated protocols. PURPOSE: To evaluate the diagnostic performance of abbreviated MRI (A-MRI) for the post-treatment evaluation of RC patients. MATERIAL AND METHODS: This retrospective study included RC patients who underwent non-contrast rectal MRI and standard liver MRI, as well as abdominal contrast-enhanced computed tomography (CECT) for post-treatment evaluation. A-MRI comprised diffusion-weighted imaging (DWI) and T2-weighted imaging of the upper abdomen and the pelvic cavity. Three radiologists independently reviewed A-MRI, CECT, and standard liver MRI in the detection of viable disease. The diagnostic performances were compared using a reference standard considering all available information, including pathology, FDG-PET, endoscopic results, and clinical follow-up. RESULTS: We included 78 patients (50 men, 28 women; mean age=60.9 ± 10.2 years) and observed viable disease in 34 (43.6%). On a per-patient-basis analysis, A-MRI showed significantly higher sensitivity (95% vs. 81%, P = 0.04) and higher accuracy (93% vs. 82%, P < 0.01), compared to those of CECT, while A-MRI showed comparable sensitivity (91% vs. 91%, P = 0.42) and accuracy (97% vs. 98%, P = 0.06) to that of standard liver MRI. On a per-lesion-based analysis, A-MRI exhibited significantly superior lesion detectability than that of CECT (figure of merit 0.91 vs. 0.77, P < 0.01) and comparable to that of standard liver MRI (figure of merit 0.91 vs. 0.92, P = 0.75). CONCLUSION: A-MRI exhibited higher sensitivity and diagnostic accuracy than those of CECT in the post-treatment evaluation of RC, while it showed comparable performances with standard liver MRI. A-MRI provides diagnostic added value in the follow-up of RC patients.

Biomarkers for predicting type 2-high and uncontrolled asthma in real-world practice.

BACKGROUND: Blood eosinophil count (BEC), immunoglobulin (Ig) E, and fractional exhaled nitric oxide (FeNO) are key clinical indicators for identifying type 2 (T2) asthma. OBJECTIVE: To provide optimal cutoff points of T2 markers for assessing T2-high or uncontrolled asthma in real-world practice. METHODS: Various clinical and laboratory parameters were analyzed according to the result of T2 markers (BEC, serum-free IgE, and FeNO) in adults with asthma who had maintained antiasthmatic medications. The cutoff levels for representing uncontrolled asthma were determined using receiver operating characteristic analysis. Blood levels of periostin and eosinophil-derived neurotoxin were measured by enzyme-linked immunosorbent assay. Activation markers of circulating eosinophils (Siglec8+) and neutrophils (CD66+) were analyzed by flow cytometry. RESULTS: Of 133 patients with asthma, 23 (17.3%) had 3 T2 markers (BEC ≥ 300 cells/µL, serum-free IgE ≥ 120 ng/mL, and FeNO ≥ 25 parts per billion) and significantly higher levels of sputum eosinophils, blood eosinophil-derived neurotoxin, and Siglec8+ eosinophils but lower 1-second forced expiratory volume percentage, in addition to a higher rate of uncontrolled status (P < .05 for all). Furthermore, patients with uncontrolled asthma had significantly higher levels of FeNO and BEC with lower 1-second forced expiratory volume percentage (P < .05 for all). The optimal cutoff values for predicting uncontrolled asthma were found to be 22 parts per billion of FeNO levels, 161.4 cells/L of BECs, and 85.9 ng/mL of serum-free IgE levels. CONCLUSION: We suggest the optimal cutoff values of BEC, IgE, and FeNO for classifying T2-high or uncontrolled asthma, which could be applied as candidate biomarkers for targeting patients with asthma who require T2 biologics.

The Hospitalist-Oncologist co-ManagemEnt (HOME) system improves hospitalization outcomes of patients with cancer.

BACKGROUND: The hospitalist system has been introduced to improve the quality and safety of inpatient care. As its effectiveness has been confirmed in previous studies, the hospitalist system is spreading in various fields. However, few studies have investigated the feasibility and value of hospitalist-led care of patients with cancer in terms of quality and safety measures. This study aimed to evaluate the efficacy of the Hospitalist-Oncologist co-ManagemEnt (HOME) system. METHODS: Between January 1, 2019, and January 31, 2021, we analyzed 591 admissions before and 1068 admissions after the introduction of HOME system on January 1, 2020. We compared the length of stay and the types and frequencies of safety events between the conventional system and the HOME system, retrospectively. We also investigate rapid response system activation, cardiopulmonary resuscitation, unplanned intensive care unit transfer, all-cause in-hospital mortality, and 30-day re-admission or emergency department visits. RESULTS: The average length of stay (15.9 days vs. 12.9 days, P < 0.001), frequency of safety events (5.6% vs. 2.8%, P = 0.006), rapid response system activation (7.3% vs. 2.2%, P < 0.001) were significantly reduced after the HOME system introduction. However, there was no statistical difference in frequencies of cardiopulomonary resuscitation and intensive care unit transfer, all-cause in-hospital morality, 30-day unplanned re-admission or emergency department visits. CONCLUSIONS: The study suggests that the HOME system provides higher quality of care and safer environment compared to conventional oncologist-led team-based care, and the efficiency of the medical delivery system could be increased by reducing the hospitalization period without increase in 30-day unplanned re-admission.

Immediate intravenous iron administration improves anaemia recovery following total knee arthroplasty: A propensity-matched analysis.

BACKGROUND AND OBJECTIVES: Patients who undergo total knee arthroplasty (TKA) have a risk of postoperative anaemia. This observational study evaluated whether single-dose intravenous ferric carboxymaltose (FCM) administered immediately after TKA facilitates the correction of anaemia. MATERIALS AND METHODS: We retrospectively analysed 722 patients who underwent primary TKA. The FCM group receiving 1000 mg intravenous FCM within one postoperative hour was compared with the non-FCM group that did not receive the medication. A propensity score matching with multiple logistic regression analysis was used to minimize intergroup differences in the baseline characteristics and postoperative blood loss. The rate and severity of postoperative anaemia were compared between the groups, along with haemoglobin (Hb) value, transfusion rate and complications. RESULTS: After propensity score matching, 231 patients were included in each group. In the FCM group, the rate of anaemia at postoperative day (POD) 7 (p = 0.021) and postoperative week (POW) 5 (p < 0.001) and the transfusion rate were significantly lower (p = 0.008). The rate of moderate to severe anaemia at POW-5 was also significantly lower in the FCM group (p < 0.001). In patients without preoperative anaemia (n = 322), the transfusion rate and rate and severity of anaemia at POD-7 and POW-5 were significantly lower in the FCM group than in the non-FCM group. CONCLUSION: Postoperative intravenous FCM administration facilitated recovery of surgery-related anaemia by improving Hb and may reduce the need for transfusion in TKA patients. Preoperative non-anaemic patients could also benefit from accelerated recovery by intravenous iron treatment.

Short-term high-dose intravenous iron reduced peri-operative transfusion after staggered bilateral total knee arthroplasty: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Staggered bilateral total knee arthroplasty, two procedures performed 4-7 days apart during a single hospitalization, has an increased risk of blood transfusion. This observational study aimed to evaluate whether immediate post-operative single, high-dose intravenous iron supplementation could reduce transfusion requirements and facilitate anaemia recovery in patients. MATERIALS AND METHODS: We retrospectively analysed 131 patients who underwent staggered bilateral total knee arthroplasty. The ferric carboxymaltose (FCM) group received 1000 mg of FCM after the first operation. The non-FCM group did not receive intravenous iron. The transfusion rate and post-operative complications were compared between the groups. The anaemia rate was evaluated pre-operatively, during hospitalization, and 5 weeks after the second total knee arthroplasty. RESULTS: The FCM group comprised 78 patients (59.5%). The rate (21.8% vs. 47.2%, p = 0.004) and amount of transfusion (0 [0-2] vs. 0 [0-0], p = 0.001) was significantly lower in the FCM group than in the non-FCM group. Although both groups' pre-operative haemoglobin concentrations were not significantly different, the FCM group demonstrated higher haemoglobin values 5 weeks post surgery (12.25 ± 0.83 mg/dl vs. 11.48 ± 1.36 mg/dl, p < 0.001). More non-FCM patients developed moderate to severe anaemia at 5 weeks post surgery (p < 0.001). The mortality and complication rates were not significantly different. CONCLUSIONS: Immediate post-operative, high-dose, intravenous iron treatment may contribute to reduced transfusion rates, facilitate haemoglobin recovery after staggered bilateral total knee arthroplasty, and minimize the development of moderate to severe anaemia.

LI-RADS Version 2018 Targetoid Appearances on Gadoxetic Acid-Enhanced MRI: Interobserver Agreement and Diagnostic Performance for the Differentiation of HCC and Non-HCC Malignancy.

BACKGROUND. In LI-RADS version 2018, observations showing at least one of five targetoid appearances in different sequences or postcontrast phases are categorized LR-M, indicating likely non-hepatocellular carcinoma (HCC) malignancy. OBJECTIVE. The purpose of this study was to evaluate interobserver agreement for LI-RADS targetoid appearances among a large number of radiologists of varying experience and the diagnostic performance of targetoid appearances for differentiating HCC from non-HCC malignancy. METHODS. This retrospective study included 100 patients (76 men, 24 women; mean age, 58 ± 9 [SD] years) at high risk of HCC who underwent gadoxetic acid-enhanced MRI within 30 days before hepatic tumor resection (25 randomly included patients with non-HCC malignancy [13, intrahepatic cholangiocarcinoma; 12, combined HCC-cholangiocarcinoma]; 75 matched patients with HCC). Eight radiologists (four more experienced [8-15 years]; four less experienced [1-5 years]) from seven institutions independently assessed observations for the five targetoid appearances and LI-RADS categorization. Interobserver agreement and diagnostic performance for non-HCC malignancy were evaluated. RESULTS. Interobserver agreement was poor for peripheral washout (κ = 0.20); moderate for targetoid transitional phase or hepatobiliary phase appearance (κ = 0.33), delayed central enhancement (κ = 0.37), and targetoid restriction (κ = 0.43); and substantial for rim arterial phase hyperenhancement (κ = 0.61). Agreement was fair for at least one targetoid appearance (κ = 0.36) and moderate for at least two, three, or four targetoid appearances (κ = 0.43-0.51). Agreement for individual targetoid appearances was not significantly different between more experienced and less experienced readers other than for targetoid restriction (κ = 0.63 vs 0.43; p = .001). Agreement for at least one targetoid appearance was fair among more experienced (κ = 0.29) and less experienced (κ = 0.37) reviewers. Agreement for at least two, three, or four targetoid appearances was moderate to substantial among more experienced reviewers (κ = 0.45-0.63) and moderate among less experienced reviewers (κ = 0.42-0.56). Existing LR-M criteria of at least one targetoid appearance had median accuracy for non-HCC malignancy of 62%, sensitivity of 84%, and specificity of 54%. For all reviewers, accuracy was highest when at least three (median accuracy, 79%; sensitivity, 68%; specificity, 82%) or four (median accuracy, 80%; sensitivity, 54%; specificity, 88%) targetoid appearances were required. CONCLUSION. Targetoid appearances and LR-M categorization exhibited considerable interobserver variation among both more and less experienced reviewers. CLINICAL IMPACT. Requiring multiple targetoid appearances for LR-M categorization improved interobserver agreement and diagnostic accuracy for non-HCC malignancy.

Outcome of No-Touch Radiofrequency Ablation for Small Hepatocellular Carcinoma: A Multicenter Clinical Trial.

Background Recently introduced no-touch radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) has the potential to improve local tumor control. Purpose To evaluate midterm clinical outcomes of monopolar no-touch RFA in single HCCs 2.5 cm or smaller. Materials and Methods In this multicenter clinical trial (ClinicalTrials.gov: NCT03375281), participants were evaluated for eligibility from November 2017 to January 2019. Patients with single HCCs 2.5 cm or smaller planning to be treated with no-touch RFA were enrolled. The rate of successful no-touch RFA, defined as performing RFA without violation of the tumor itself, was recorded. Multivariable logistic regression analysis was used to determine associated factors for failure of no-touch RFA. Development of major complication after no-touch RFA was also recorded. Cumulative incidence of local tumor progression (LTP) and recurrence-free survival were estimated by using the Kaplan-Meier method. Results A total of 140 participants (mean age, 62 years ± 9 [standard deviation]; 106 men) were evaluated. No-touch RFA was successfully performed in 128 participants (128 of 140; 91.4%), and conversion to tumor puncture RFA was undertaken in 12 participants because of the lack of a safe access route. By using either no-touch RFA or conversion to tumor puncture RFA, all participants achieved technical success of RFA, which was defined as complete coverage of target tumor by ablation zone. Insufficient peritumoral parenchyma (<5 mm width around more than half portion of tumor; odds ratio, 74; 95% CI: 18, 309; P < .001) was the only significant predictive factor for failure of the no-touch technique. Among the 140 participants, LTP developed in two participants, and the estimated 1- and 2-year cumulative incidence of LTP was 0.7% and 1.6%, respectively. The estimated 1- and 2-year recurrence-free survival was 82.8% and 74.1%, respectively. Conclusion No-touch radiofrequency ablation was an effective and safe treatment method for small hepatocellular carcinomas (≤2.5 cm), with 1.6% of cumulative incidence of local tumor progression at 2 years. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Soulen and García-Mónaco in this issue.

Interobserver Variability and Diagnostic Performance of Gadoxetic Acid-enhanced MRI for Predicting Microvascular Invasion in Hepatocellular Carcinoma.

Background Accurate identification of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) before treatment is critical for selecting a proper treatment strategy. Purpose To evaluate the interobserver agreement and the diagnostic performance of the MRI assessment of MVI in HCC according to the level of radiologist experience. Materials and Methods This retrospective study included 100 patients with surgically confirmed HCCs smaller than 5 cm who underwent gadoxetic acid-enhanced MRI between 2013 and 2016. Eight postfellowship radiologists (four with 7-13 years of experience [more experienced] and four with 3-6 years of experience [less experienced]) evaluated four imaging features (nonsmooth tumor margin, irregular rim-like enhancement in the arterial phase, peritumoral arterial phase hyperenhancement, peritumoral hepatobiliary phase hypointensity) and assigned the possibility of MVI. Interobserver agreement was determined by using Fleiss κ statistics according to reviewer experience and tumor size (≤3 cm vs >3 cm). With reference standards of histopathologic specimens, the diagnostic performance in the identification of MVI was assessed by using receiver operating characteristic curve analysis. Results In 100 patients (mean age, 58 years ± 10 [standard deviation]; 70 men) with 100 HCCs (mean size, 2.8 cm ± 0.9), 39 (39%) HCCs had MVI. The overall interobserver agreement was fair to moderate for the imaging features and their combinations (κ = 0.38-0.47) and MVI probability (κ = 0.41; 95% confidence interval: 0.33, 0.45). More experienced reviewers demonstrated higher agreement in MVI probability than less experienced reviewers (κ = 0.55 vs 0.36, respectively; P = .002). Diagnostic performance of each reviewer was modest for MVI prediction (area under the receiver operating characteristic curve [AUC] range, 0.60-0.74). The AUCs for the diagnosis of MVI were lower for HCCs larger than 3 cm (range, 0.55-0.69) than for those less than or equal to 3 cm (range, 0.59-0.75). Conclusion Considerable interobserver variability exists in the assessment of microvascular invasion in hepatocellular carcinoma using MRI, even for more experienced radiologists. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Tang in this issue.

Radiologic-Pathologic Correlation of Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement at Gadoxetic Acid-enhanced MRI: A Multicenter Study.

Background Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) at gadoxetic acid-enhanced MRI may indicate hepatocellular carcinoma (HCC) or nonmalignant cirrhosis-associated nodules. Purpose To assess the distribution of pathologic diagnoses of HBP hypointense nodules without APHE at gadoxetic acid-enhanced MRI and to evaluate clinical and imaging features in differentiating their histologic grades. Materials and Methods This retrospective multicenter study included pathologic analysis-confirmed HBP hypointense nodules without APHE (≤30 mm) in patients with chronic liver disease or cirrhosis screened between January 2008 and June 2016. Central pathologic review by 10 pathologists determined final histologic grades as progressed HCC, early HCC, high-grade dysplastic nodule (DN), and low-grade DN or regenerative nodule. Gadoxetic acid-enhanced MRI features were analyzed by three radiologists. Multivariable logistic regression analyses with elastic net regularization were performed to identify clinical and imaging features for differentiating histologic grades. Results There were 298 patients (mean age, 59 years ± 10; 226 men) with 334 nodules evaluated, and progressed HCCs were diagnosed in 44.0% (147 of 334), early HCCs in 20.4% (68 of 334), high-grade DNs in 27.5% (92 of 334), and low-grade DNs or regenerative nodules in 8.1% (27 of 334). Serum α-fetoprotein level 100 ng/mL or greater (odds ratio, 2.7; P = .01) and MRI features including well-defined margin (odds ratio, 5.5; P = .003), hypointensity at precontrast T1-weighted imaging (odds ratio, 3.2; P < .001), intermediate hyperintensity at T2-weighted imaging (odds ratio, 3.4; P < .001), and restricted diffusion (odds ratio, 1.9; P = .04) were independent predictors for progressed HCC at multivariable analysis. Conclusion In patients at high risk for hepatocellular carcinoma (HCC), hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid-enhanced MRI corresponded mainly to progressed HCCs, early HCCs, and high-grade dysplastic nodules. High α-fetoprotein level and some imaging features at MRI helped to differentiate progressed HCC from lower grade nodules. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Motosugi in this issue.

Suppression of Mig-6 overcomes the acquired EGFR-TKI resistance of lung adenocarcinoma.

BACKGROUND: The resistance of lung cancer to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the unconquered frontiers in chemotherapy. Mitogen-inducible gene 6 (Mig-6) is known to inhibit the kinase activity of epidermal growth factor receptor (EGFR). Similarly, numerous studies of mouse models suggested tumor suppressive function of Mig-6 in lung cancer. On the contrary, the results of clinical investigations revealed that lung cancer patients with elevated expression of Mig-6 are associated with a poor prognosis. More recent work showed that unlike wild type (WT) EGFR, mutant EGFR phosphorylates Mig-6 and phosphorylated Mig-6 negatively regulates the degradation of EGFR mutants in lung adenocarcinoma. Here, we tried to untangle the controversies surrounding Mig-6 function as a protagonist or an antagonist of EGFR-TKI resistant lung cancer. METHODS: We compared the expression and phosphorylation status of Mig-6 in the EGFR-TKI resistant lung adenocarcinoma (PC9/GR cells) to EGFR-TKI sensitive lung adenocarcinoma (PC9 cells). We investigated the function of Mig-6 by either depletion or overexpression of Mig-6 in those cells and evaluated the efficacy of combining of Mig-6 knock-down and EGFR-TKI treatment in PC9/GR. The correlation between Mig-6 expressions and the prognoses of lung adenocarcinoma was examined by The Cancer Genome Atlas (TCGA) data and clinical samples. RESULTS: Our results indicated that the expression of Mig-6 was significantly increased in PC9/GR cells compared to that of PC9 cells. The significant portion of Mig-6 existed as a phosphorylated form in PC9 and PC9/GR cells. Moreover, overexpression of Mig-6 significantly increased the cell proliferation, invasion and epithelial mesenchymal transition (EMT) in PC9 cells. Combination of Mig-6 knock-down and EGFR-TKI treatment significantly overcame the EGFR-TKI resistance of PC9/GR cells. In addition, our analyses of clinical samples confirmed that high Mig-6 expressions positively correlate with a poor prognosis and EGFR-TKI resistance in lung adenocarcinoma. CONCLUSION: Our findings reinforce scientific notion of Mig-6 as an oncoprotein in the context of EGFR-TKI resistant lung adenocarcinoma. We propose that targeting Mig-6 may be a promising strategy to overcome the EGFR-TKI resistance in lung cancer.

Partial oxidation of methane to methanol by isolated Pt catalyst supported on a CeO2 nanoparticle.

Catalytic transformation of methane (CH4) into methanol in a single step is a challenging issue for the utilization of CH4. We present a direct method for converting CH4 into methanol with high selectivity over a Pt/CeO2 catalyst which contains ionic Pt2+ species supported on a CeO2 nanoparticle. The Pt/CeO2 catalyst reproducibly yielded 6.27 mmol/g of Pt with a selectivity of over 95% at 300 °C when CH4 and CO are used as reactants, while the catalyst had a lower activity when using only CH4 without CO. Active lattice oxygen created on the Pt and CeO2 interface provides selective reaction pathways for the conversion of CH4 to methanol. Based on high-angle annular dark-field scanning transmission electron microscopy, x-ray photoelectron spectroscopy, x-ray absorption near-edge structure, extended x-ray absorption fine structure, catalytic studies, and density functional theory calculations, we propose a mechanistic pathway involving CH4 activation at the active site in the vicinity of Pt2+ species.

Optimization of the Operating Room Scheduling Process for Improving Efficiency in a Tertiary Hospital.

Efficient operating room (OR) scheduling can improve OR utilization and reduce costs. We hypothesize that the scheduling office (ORSO) leading the modification scheduling process could increase OR utilization rate. Using retrospective data from a single tertiary hospital in two consecutive calendar years, we compared OR utilization rate, the number of daily cases and cumulative operative time in the pre- and post-implementation of scheduling process alteration. We operated about 100,609 cases in the OR during the study period. Daytime utilization rate increased from 85.6% to 89.4% (P < 0.001); overall OR utilization rate from 115.1% to 117.6% (P = 0.019); daily case numbers from 229.9 ± 7.3 to 239.6 ± 7.6 (P = 0.0.14); and cumulative operation time of total and daytime cases from 611.7 case-hour/day to 624.5 case-hour/day (P = 0.013) and from 510.8 case-hour/day to 533.8 case-hour/day (P < 0.001), respectively. Evening/night time case-hour significantly decreased from 100.9 case-hour/day to 90.7 case-hour/day (P < 0.001). The optimization of the scheduling process and coordination by the office during regular workhours resulted in enhanced OR efficiency. The OR scheduling office can act as a control tower to make OR management more flexible, which can improve efficiency and carry financial benefits in tertiary hospitals.

Efficacy of Vinorelbine Monotherapy as Third- or Further-Line Therapy in Patients with Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: The survival rate of patients with lung cancer has increased significantly over the years, but there has been no further progress in third- or fourth-line therapy. We investigated the efficacy and tolerability of monotherapy with weekly vinorelbine, a semi-synthetic vinca alkaloid, in advanced non-small-cell lung cancer (NSCLC) patients who had previously been treated several times. METHODS: In all, 159 NSCLC patients who received vinorelbine monotherapy as third- or further-line therapy between January 2008 and July 2017 were included in this study. Patients received vinorelbine intravenously at a dose of 25-30 mg/m2/week. RESULTS: Their mean age was 62.4 years. The histologic types of tumor were adenocarcinoma (50.9%), squamous cell carcinoma (42.8%), and others (6.2%). The overall response rate was 19.5% (31/159). The median progression-free survival (PFS) was 3.0 months (95% confidence interval [CI] 2.5-3.5 months), and the median overall survival (OS) after vinorelbine use was 7.6 months (95% CI 6.2-9.0 months). Vinorelbine therapy showed significantly higher efficacy in patients with adenocarcinoma, and these patients had a longer PFS than patients with other types of cancer. Patients who received vinorelbine as fifth- or further-line treatment had a higher response rate and longer PFS and OS than those who received vinorelbine as third- or fourth-line treatment. CONCLUSIONS: Weekly vinorelbine monotherapy may be a feasible therapeutic option for patients with heavily treated, advanced NSCLC, particularly lung adenocarcinoma.

Propofol for implantable cardioverter defibrillator implantation in patients with Brugada syndrome.

AIMS: Avoiding propofol in patients with Brugada syndrome has been suggested because of the theoretical risk of provoking ventricular arrhythmias, although propofol may be selected for conscious sedation during electrophysiological procedures in catheterization laboratories. This study aimed to document periprocedural electrocardiographic changes and adverse events in patients with Brugada syndrome undergoing implantable cardioverter defibrillator (ICD) implantation using propofol sedation. METHODS: We reviewed the clinical data of 53 consecutive patients who underwent ICD implantation during 1998-2011. Sedation was achieved by combining propofol with either midazolam or fentanyl, and a bolus propofol dose (0.5-1 mg/kg) was administered to induce deep sedation. Periprocedural events, including arrhythmias, defibrillations, and hyperthermia episodes, were evaluated, and electrocardiogram (ECG) variables were measured. The need for emergency anesthetic support/intubation and incidence of perioperative complications or mortality were analyzed. RESULTS: Procedure time and cumulative propofol dose for each patient was 125.2 (42.8) min and 204.6 (212.7) mg, respectively. During deep sedation, blood pressure, heart rate, and oxygen saturation were significantly decreased (P < 0.001) such that eight (15.1%) patients required manual ventilation and one (1.9%) needed atropine injection. No significant ECG changes were observed. Only two (3.7%) patients showed newly developed ST elevation in the anterior precordial lead, whereas three (5.6%) had isolated premature ventricular contractions. CONCLUSION: ICD implantation without significant ECG changes or adverse outcomes is feasible under propofol sedation in patients with Brugada syndrome. However, because of significant hemodynamic changes and respiratory compromise, close monitoring and meticulous propofol dose titration is warranted.

Information-seeking tactics and sense of workplace community in Korea.

This research examined how information-seeking tactics and sense of workplace community are related to one another. Data from Korea showed that workers (n = 314) who preferred overt tactics of seeking information (i.e., direct questioning) also reported a stronger sense of workplace community. Information types and sources did not moderate the relationship between information-seeking tactics and sense of workplace community. Information types, however, moderated the relationship between importance of information and sense of workplace community and the relationship between coworker availability as an information source and sense of workplace community.

Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma.

Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients. It also has changed the concept of conventional anti-cancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways. Recent studies demonstrated that PD-L1 expression is significantly correlated to the mutation status of EGFR, and activation of EGFR signaling can also induce the expression of PD-L1. However, the real linker between PD-L1 and EGFR signaling remains to be revealed. Our previous study revealed that the Hippo pathway effector YAP confers EGFR-TKI resistance in lung adenocarcinoma, and inhibition of YAP restores sensitivity to EGFR-TKIs. Thus, we examined whether PD-L1 is relevant, in terms of conferring EGFR-TKI resistance and whether YAP directly regulates the expression of PD-L1 in this context. First, we compared the expression levels of PD-L1 and YAP between EGFR-TKI-resistant PC9 cells and the parental PC9 adenocarcinoma cells. The expression levels of both YAP and PD-L1 were markedly higher in the EGFR-TKI-resistant cells compared to the parental cells, suggesting differential expression pattern between two cell types. YAP knockdown significantly decreased the expression of PD-L1 in the EGFR-TKI-resistant cells, while YAP overexpression increased the expression of PD-L1 in the parental PC9 cells. Then, our results revealed that YAP regulates the transcription of PD-L1, and the YAP/TEAD complex binds to the PD-L1 promoter. Surprisingly, knockdown of PD-L1 was sufficient to decrease cell proliferation and wound healing in the EGFR-TKI-resistant PC9 cells. These data suggest a PD1-independent oncogenic function of PD-L1. The Hippo effector YAP plays a crucial role in linking the PD-L1 and EGFR-TKI resistance by directly regulating the expression of PD-L1 in lung cancer. Targeting PD-L1 directly or via YAP could provide an effective therapeutic strategy for EGFR-TKI-resistant lung adenocarcinoma.

Doppler Ultrasound in Liver Cirrhosis: Correlation of Hepatic Artery and Portal Vein Measurements With Model for End-Stage Liver Disease Score.

OBJECTIVES: To determine whether hepatic arterial and portal venous Doppler ultrasound measurements of the liver in cirrhotic patients correlate with patients' Model for End-Stage Liver Disease (MELD) scores, splenomegaly, or ascites. MATERIALS AND METHODS: Sonographic images and reports were reviewed of 264 patients with hepatic cirrhosis who underwent abdominal ultrasound with Doppler in this internal review board-approved retrospective study. MELD scores were recorded at the time of ultrasound. On gray-scale ultrasound, spleen length was measured and the presence of ascites was noted. Hepatic arterial velocity (HAv) with angle correction, hepatic arterial resistive index, and portal vein velocity with angle correction were measured on Doppler ultrasound. Correlation of hepatic arterial and portal venous Doppler values with MELD score, presence of splenomegaly, and presence of ascites was tested using linear or binary logistic regression analysis. Diagnostic performance of Doppler parameters for high-risk MELD was assessed. RESULTS: The HAv statistically significantly correlated with the MELD score (P = .0001), spleen size (P =.027), and presence of ascites (P =.0001), whereas the hepatic arterial resistive index and portal vein velocity did not correlate with these factors. For MELD scores greater than 19, an HAv greater than 120 cm/s showed accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 74, 42, 90, 67, and 76%, respectively. With an HAv greater than 160 cm/s, the odds ratio for MELD scores greater than 19 was 42.1. CONCLUSIONS: We found a statistically significant correlation with elevated HAv and increasing MELD scores, splenomegaly, and presence of ascites in patients with cirrhotic liver disease; this may be a useful imaging biomarker in the evaluation of patients with cirrhosis.

Visibility of focal liver lesions: Comparison between kupffer phase of CEUS with sonazoid and hepatobiliary phase of gadoxetic acid-enhanced MRI.

BACKGROUND: To investigate the agreement between Kupffer phase of Sonazoid contrast-enhanced sonography (CEUS) and hepatobiliary phase of gadoxetic acid-enhanced MRI in the evaluation of focal liver lesions (FLLs). METHODS: One hundred fifty-four FLLs in 154 patients who underwent both Sonazoid CEUS and gadoxetic acid-enhanced liver MRI were included in this retrospective study. FLL visibility on the Kupffer-phase images was graded as one (invisible or isoenhancing), two (vaguely visible or vaguely hypoenhancing), or three (clearly visible or clearly hypoenhancing), and that on the hepatobiliary-phase images of MRI was graded as one (invisible or hyper/isointense), two (vaguely visible or weakly hypointense), or three (clearly visible or strongly hypointense). Pairwise comparison of lesion visibility between the two modalities was performed, and intermodality agreement was assessed. RESULTS: On Kupffer-phase CEUS, 31 (20.1%) lesions were invisible, 17 (11.1%) were vaguely visible, and 106 (68.9%) were clearly visible. On the hepatobiliary-phase MRI, 9 (5.9%) lesions were invisible, 45 (29.2%) were vaguely visible, and 100 (64.9%) were clearly visible. Overall, lesion visibility scores were not significantly different between the two modalities (p = 0.121), but the visibility was significantly better on MRI in smaller lesions. Twenty-eight lesions (18.2%) showed discrepancy in the visibility on CEUS and MRI, and most of the cases (89.7%) were lesions that were invisible on CEUS but visible on MRI. CONCLUSIONS: The overall visibility of FLLs was comparable between the Kupffer phase of Sonazoid-CEUS and the hepatobiliary-phase images of gadoxetic acid-enhanced MRI, with a discrepancy between the two modalities in 18% of the cases. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:542-550, 2017.