Using nomogram of the Barcelona Clinic Liver Cancer system for treatment selection in patients with stage C hepatocellular carcinoma

Abstract Background The nomogram of the Barcelona Clinic Liver Cancer (BCLC) for hepatocellular carcinoma (HCC) has been used for outcome prediction. Patients with BCLC stage C HCC often undergo anti-cancer therapy against current treatment guidelines in real world practice. We aimed to use the nomogram to provide guidance on treatment selection for BCLC stage C patients. Methods A total of 1317 patients with stage C HCC were retrospectively analyzed and divided into four groups by nomogram points. One-to-one matched pairs between patients receiving different treatments were generated by the propensity score with matching model within these groups. Survival analysis was performed by Kaplan-Meier method with log-rank test. Results Patients with higher nomogram points were more often treated with targeted or supportive therapies (p  15, there was no significant difference in survival between patients receiving two different treatment strategies. Conclusions The nomogram of BCLC system is a feasible tool to help stage C HCC patients to select primary anti-cancer treatment in pursuance of better overall survival.https://deepblue.lib.umich.edu/bitstream/2027.42/142787/1/12885_2018_Article_4202.pd

Albuminâ bilirubin gradeâ based nomogram of the BCLC system for personalized prognostic prediction in hepatocellular carcinoma

Background & AimsThe prognostic accuracy of individual hepatocellular carcinoma (HCC) patient in each Barcelona Clinic Liver Cancer (BCLC) stage is unclear. We aimed to develop and validate an albuminâ bilirubin (ALBI) gradeâ based nomogram of BCLC to estimate survival for individual HCC patient.MethodsBetween 2002 and 2016, 3690 patients with newly diagnosed HCC were prospectively enrolled and retrospectively analysed. Patients were randomly split into derivation and validation cohort by 1:1 ratio. Multivariate Cox proportional hazards model was used to generate the nomogram from tumour burden, ALBI grade and performance status (PS). The concordance index and calibration plot were determined to evaluate the performance of this nomogram.ResultsBeta coefficients from the Cox model were used to assign nomogram points to different degrees of tumour burden, ALBI grade and PS. The scores of the nomogram ranged from 0 to 24, and were used to predict 3â and 5â year patient survival. The concordance index of this nomogram was 0.77 (95% confidence interval [CI]: 0.71â 0.81) in the derivation cohort and 0.76 (95% CI: 0.71â 0.81) in the validation cohort. The calibration plots to predict both 3â and 5â year survival rate well matched with the 45â degree ideal line for both cohorts, except for ALBIâ based BCLC stage 0 in the validation cohort.ConclusionsThe proposed ALBIâ based nomogram of BCLC system is a simple and feasible strategy in the precision medicine era. Our data indicate it is a straightforward and userâ friendly prognostic tool to estimate the survival of individual HCC patient except for very early stage patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153250/1/liv14249_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153250/2/liv14249.pd

BSRS-5 (5-item Brief Symptom Rating Scale) scores affect every aspect of quality of life measured by WHOQOL-BREF in healthy workers

This study aims to evaluate and quantify the possible effect of psychological symptoms on healthy workers' quality of life (QOL). The workers were recruited from a factory in south Taiwan. We assessed their psychological symptoms with a 5-item brief symptom rating scale (BSRS-5) and measured the QOL using the Taiwanese version of the World Health Organization Quality of Life (WHOQOL)-BREF. Multiple linear regression analysis was conducted to explore the association between the two tools after control of confounding by other predictors. A total of 1,080 workers , who attended a physical examination, completed questionnaires and informed consent forms. Scores on the BSRS-5 significantly predicted scores in each domain and items of the WHOQOL-BREF. The magnitude of psychological domain score seemed to be affected the most; every 1 point increase in BSRS-5 was associated with a 0.39 raw score (equivalent to 2. 44 percentile) decrease in QOL. The sleep facet of WHOQOL appeared to have the highest association, followed by items of negative feelings, energy, and concentration. The BSRS-5 score is predictive for scores of all four domains and 26 items of the Taiwanese version of the WHOQOL-BREF for regular factory workers

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Tracking Controller Design for Diving Behavior of an Unmanned Underwater Vehicle

The study has investigated the almost disturbance decoupling problem of nonlinear uncertain control systems via the fuzzy feedback linearization approach. The significant dedication of this paper is to organize a control algorithm such that the closed-loop system is active for given initial condition and bounded tracking trajectory with the input-to-state stability and almost disturbance decoupling performance. This study presents a feedback linearization controller for diving control of an unmanned underwater vehicle. Unmanned underwater vehicle proposes difficult control subject due to its nonlinear dynamics, uncertain models, and the existence of disturbances that are difficult to measure. In general, while investigating the diving dynamics of an unmanned underwater vehicle, the pitch angle is always assumed to be small. This assumption is a strong restricting constraint in many interesting practical applications and will be relaxed in this study

Eritoran Attenuates Hepatic Inflammation and Fibrosis in Mice with Chronic Liver Injury

Toll-like receptor 4 (TLR4) signaling plays a key role in liver inflammation and fibrosis. The therapeutic effects of eritoran, a TLR4 antagonist, in mice with chronic liver injury remained unclear. C57BL/6 mice were fed a fast-food diet (FFD) or treated with carbon tetrachloride (CCl4) to induce chronic liver injury. Eritoran (10 mg/kg) or a vehicle was randomly intraperitoneally administered to the FFD-fed mice and the CCl4-injured mice. Primary mouse liver cells were cultured with lipopolysaccharide (LPS) or eritoran. In both FFD and CCl4 mouse models, eritoran significantly reduced serum ALT levels and decreased hepatic inflammatory cell infiltration without altering hepatic steatosis. Additionally, eritoran attenuated liver fibrosis by decreasing hepatic stellate cells (HSCs) activation and the abundance of α-smooth muscle actin and transforming growth factor-β1. Hepatic TLR4 downstream signaling including MyD88 expression, NF-κB p65 nuclear translocation, p38 and JNK phosphorylation were successfully inhibited by eritoran. In the in vitro study, LPS-induced nuclear translocation of NF-κB in primary HSCs and Kupffer cells was significantly suppressed by eritoran. In conclusion, eritoran attenuated hepatic inflammation and fibrosis by inhibition of the TLR4 signaling pathway in mice with chronic liver injury. Eritoran may serve as a potential drug for chronic liver disease

Hepatocellular Carcinoma Patients With Performance Status 1 Deserve New Classification and Treatment Algorithm in the BCLC System

Hepatocellular carcinoma (HCC) patients with performance status (PS) 1 or 2 are considered similar in the Barcelona Clinic Liver Cancer (BCLC) system. The rationales are not fully studied. A total of 693 and 335 HCC patients were classified as PS 1 and 2, respectively, in a prospectively followed up database. One-to-one matched pairs between HCC patients were generated by using the propensity score with matching model. Survival analysis was performed and the hazard ratio was calculated with the Cox proportional hazards model. Patients with PS 1 were significantly younger and had better liver and renal functions compared with patients with PS 2 (all P 0.05); patients with PS 1 had significantly better prognosis compared with patients with PS 2 (P < 0.05). There were 68% of patients with PS 1 that underwent aggressive treatments (resection, transplantation, percutaneous ablation, or transarterial chemoembolization), which were significantly correlated to better outcome with a hazard ratio of 0.539 in the matching model (P = 0.002). For patients with PS 2, aggressive treatments were not significantly associated with better long-term survival. Aggressive treatments provide survival benefits for patients with PS 1, but not for patients with PS 2. HCC patients with PS 1 or 2 should be considered clinically different disease entities in the BCLC system