Novel biomarker-based model for the prediction of sorafenib response and overall survival in advanced hepatocellular carcinoma: a prospective cohort study

Background Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS). Methods This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib. Potential serum biomarkers (namely, hepatocyte growth factor [HGF], fibroblast growth factor [FGF], vascular endothelial growth factor receptor-1, CD117, and angiopoietin-2) were tested. After identifying independent predictors of tumor response, a risk scoring system for predicting OS was developed and 3-fold internal validation was conducted. Results A risk scoring system was developed with six covariates: etiology, platelet count, Barcelona Clinic Liver Cancer stage, protein induced by vitamin K absence-II, HGF, and FGF. When patients were stratified into low-risk (score ≤ 5), intermediate-risk (score 6), and high-risk (score ≥ 7) groups, the model provided good discriminant functions on tumor response (concordance [c]-index, 0.884) and 12-month survival (area under the curve [AUC], 0.825). The median OS was 19.0, 11.2, and 6.1 months in the low-, intermediate-, and high-risk group, respectively (P  0.05 between expected and observed values). Conclusions This new model including serum FGF and HGF showed good performance in predicting the response to sorafenib and survival in patients with advanced HCC.This work was funded by Doosan Yonkang Foundation (Grant No. 30–2016-0240), Liver Research Foundation of Korea as part of Bio Future Strategies Research Project, and Ewha Womans University research grant (2016). The funding bodies had no role in the design of the study, collection, analysis, and interpretation of data and in writing of the manuscript

Early countermeasures to COVID-19 at long-term care facilities in Gwangju Metropolitan City, Republic of Korea

Objectives The coronavirus disease 2019 (COVID-19) pandemic has continued since its first detection in the Republic of Korea on January 20, 2020. This study describes the early countermeasures used to minimize the risk of COVID-19 outbreaks during cohort quarantine and compares the epidemiological characteristics of 2 outbreaks in long-term care facilities (LTCFs) in Gwangju Metropolitan City in summer 2020. Methods An epidemiological investigation was conducted via direct visits. We investigated epidemiological characteristics, including incidence, morbidity, and mortality rates, for all residents and staff members. Demographic characteristics were analyzed using a statistical program. Additionally, the method of managing infection in LTCFs is described. Results Residents and caregivers had high incidence rates in LTCF-A and LTCF-B, respectively. LTCF-B had a longer quarantine period than LTCF-A. The attack rate was 20.02% in LTCF-A and 27.9% in LTCF-B. The mortality rate was 2.3% (1/43) in LTCF-B, the only facility in which a COVID-19 death occurred. Conclusion Extensive management requires contact minimization, which involves testing all contacts to mitigate further transmission in the early stages of LTCF outbreaks. The findings of this study can help inform and prepare public health authorities for COVID-19 outbreaks, particularly for early control in vulnerable facilities

Efficacy and safety of entecavir plus carnitine complex (GODEX®) compared to entecavir monotherapy in patient with ALT elevated chronic hepatitis B: randomized, multicenter open-label trials. The GOAL study

Background/AimsCarnitine and vitamin complex (Godex®) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients.Methods130 treatment-naïve patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months.ResultsAmong the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-γ secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment.ConclusionsALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment

Etiology of Invasive Bacterial Infections in Immunocompetent Children in Korea (1996-2005): A Retrospective Multicenter Study

The purpose of this study was to identify the major etiological agents responsible for invasive bacterial infections in immunocompetent Korean children. We retrospectively surveyed invasive bacterial infections in immunocompetent children caused by eight major pediatric bacteria, namely Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species that were diagnosed at 18 university hospitals from 1996 to 2005. A total of 768 cases were identified. S. agalactiae (48.1%) and S. aureus (37.2%) were the most common pathogens in infants younger than 3 months. S. agalactiae was a common cause of meningitis (73.0%), bacteremia without localization (34.0%), and arthritis (50%) in this age group. S. pneumoniae (45.3%) and H. influenzae (20.4%) were common in children aged 3 months to 5 yr. S. pneumoniae was a common cause of meningitis (41.6%), bacteremia without localization (40.0%), and bacteremic pneumonia (74.1%) in this age group. S. aureus (50.6%), Salmonella species (16.9%), and S. pneumoniae (16.3%) were common in older children. A significant decline in H. influenzae infections over the last 10 yr was noted. S. agalactiae, S. pneumoniae, and S. aureus are important pathogens responsible for invasive bacterial infections in Korean children

High Prevalence of Ceftazidime-Resistant Klebsiella pneumoniae and Increase of Imipenem-Resistant Pseudomonas aeruginosa and Acinetobacter spp. in Korea: a KONSAR Program in 2004

A nationwide antimicrobial resistance surveillance has been conducted since 1997 in Korea. In this study, susceptibility test data generated in 2004 by KONSAR group hospitals were analyzed and compared to those at a commercial laboratory. In hospitals, the rank orders of organisms in 2004 were identical to those in 2003. The most prevalent species was Staphylococcus aureus (20.2%) in hospitals, but Escherichia coli (29.7%) in the commercial laboratory. The proportions of Enterococcus faecium to all isolates of Enterococcus faecalis plus E. faecium were 47.2% in hospitals and 24.9% in the commercial laboratory. The mean resistance rates of significant antimicrobial-organism combinations in hospitals were: oxacillin-resistant S. aureus (68%), oxacillin-resistant (penicillin-nonsusceptible) Streptococcus pneumoniae (68%), vancomycin-resistant E. faecium (25%), cefotaxime-resistant E. coli (14%), ceftazidime- and cefoxitin-resistant Klebsiella pneumoniae (34% and 32%, respectively), and imipenem-resistant Acinetobacter spp. and Pseudomonas aeruginosa (17% and 24%, respectively). In conclusion, oxacillin-resistant staphylococci, expanded-spectrum cephalosporin-resistant K. pneumoniae, and imipenem-resistant Acinetobacter spp. and P. aeruginosa were prevalent in 2004. Increasing trends were observed for vancomycin-resistant E. faecium, cefoxitin-resistant E. coli and K. pneumoniae, and imipenem-resistant Acinetobacter spp. and P. aeruginosa. Certain antimicrobial-organism combinations were also prevalent among the commercial laboratory-tested strains

The Causative Organisms of Bacterial Meningitis in Korean Children in 1996-2005

Bacterial meningitis remains a serious cause of morbidity and mortality in childhood, despite the availability of effective vaccines against Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae. The purpose of this study was to analyze data on bacterial meningitis cases in Korea from 1996 through 2005. The information of all hospitalized bacteria-proven meningitis cases was obtained from 17 university hospitals nationwide. A total of 402 cases were identified. Of these, 125 (29.9%) cases were neonates. Streptococcus agalactiae was the most common bacteria responsible for 99 (24.6%) of all cases regardless of age, followed by S. pneumoniae for 91 (22.6%) and H. influenzae for 67 (16.7%) patients. The common etiology beyond the neonatal period was S. pneumoniae for 91 (33.0%) followed by H. influenzae for 63 (22.8%) patients. The overall case fatality rate was 9.4%, which was similar with that in 1986-1995. In conclusion, S. agalactiae, S. pneumoniae and H. influenzae were important etiologic agents of bacterial meningitis in children in the last 10 yrs. It is required to establish the preventive strategy of the three bacteria. The nationwide epidemiologic study should be continued to evaluate immunization strategy and efficacy

High inorganic phosphate intake promotes tumorigenesis at early stages in a mouse model of lung cancer

© 2015 Lee et al. Inorganic phosphate (Pi) is required by all living organisms for the development of organs such as bone, muscle, brain, and lungs, regulating the expression of several critical genes as well as signal transduction. However, little is known about the effects of prolonged dietary Pi consumption on lung cancer progression. This study investigated the effects of a highphosphate diet (HPD) in a mouse model of adenocarcinoma. K-rasLA1 mice were fed a normal diet (0.3% Pi) or an HPD (1% Pi) for 1, 2, or 4 months. Mice were then sacrificed and subjected to inductively coupled plasma mass/optical emission spectrometry and laser ablation inductively coupled plasma mass-spectrometry analyses, western blot analysis, histopathological, immunohistochemical, and immunocytochemical analyses to evaluate tumor formation and progression (including cell proliferation, angiogenesis, and apoptosis), changes in ion levels and metabolism, autophagy, epithelial-to-mesenchymal transition, and protein translation in the lungs. An HPD accelerated tumorigenesis, as evidenced by increased adenoma and adenocarcinoma rates as well as tumor size. However, after 4 months of the HPD, cell proliferation was arrested, and marked increases in liver and lung ion levels and in energy production via the tricarboxylic acid cycle in the liver were observed, which were accompanied by increased autophagy and decreased angiogenesis and apoptosis. These results indicate that an HPD initially promotes but later inhibits lung cancer progression because of metabolic adaptation leading to tumor cell quiescence. Moreover, the results suggest that carefully regulated Pi consumption are effective in lung cancer prevention

Smoking and Genetic Risk Variation Across Populations of E uropean, A sian, and A frican A merican Ancestry—A Meta‐Analysis of Chromosome 15q25

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91126/1/gepi21627.pd