Dietary Habits and Risk of Death due to Hepatocellular Carcinoma in a Large Scale Cohort Study in Japan. Univariate Analysis of JACC Study Data

IntroductionThere were almost 1 million deaths in children aged between 5 and 14 years in 2017, and pneumonia accounted for 11%. However, there are no validated guidelines for pneumonia management in older children and data to support their development are limited. We sought to understand risk factors for mortality among children aged 5–14 years hospitalised with pneumonia in district-level health facilities in Kenya.MethodsWe did a retrospective cohort study using data collected from an established clinical information network of 13 hospitals. We reviewed records for children aged 5–14 years admitted with pneumonia between 1 March 2014 and 28 February 2018. Individual clinical signs were examined for association with inpatient mortality using logistic regression. We used existing WHO criteria (intended for under 5s) to define levels of severity and examined their performance in identifying those at increased risk of death.Results1832 children were diagnosed with pneumonia and 145 (7.9%) died. Severe pallor was strongly associated with mortality (adjusted OR (aOR) 8.06, 95% CI 4.72 to 13.75) as were reduced consciousness, mild/moderate pallor, central cyanosis and older age (>9 years) (aOR >2). Comorbidities HIV and severe acute malnutrition were also associated with death (aOR 2.31, 95% CI 1.39 to 3.84 and aOR 1.89, 95% CI 1.12 to 3.21, respectively). The presence of clinical characteristics used by WHO to define severe pneumonia was associated with death in univariate analysis (OR 2.69). However, this combination of clinical characteristics was poor in discriminating those at risk of death (sensitivity: 0.56, specificity: 0.68, and area under the curve: 0.62).ConclusionChildren >5 years have high inpatient pneumonia mortality. These findings also suggest that the WHO criteria for classification of severity for children under 5 years do not appear to be a valid tool for risk assessment in this older age group, indicating the urgent need for evidence-based clinical guidelines for this neglected population.

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14-CpG-Based Signature Improves the Prognosis Prediction of Hepatocellular Carcinoma Patients

BioMed Research International ◽

10.1155/2020/9762067 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Hong-ye Jiang ◽

Gang Ning ◽

Yen-sheng Wang ◽

Wei-biao Lv

Keyword(s):

Hepatocellular Carcinoma ◽

Dna Methylation ◽

Survival Analysis ◽

Validation Cohort ◽

Univariate Analysis ◽

Prognosis Prediction ◽

Risk Of Death ◽

Ajcc Stage ◽

Patient Prognosis ◽

Robust Likelihood

Background. Epigenetic dysregulation via alteration of DNA methylation often occurs during the development and progression of cancer, including hepatocellular carcinoma (HCC). In the past, many patterns of single-gene DNA methylation have been extensively explored in the context of HCC prognosis prediction. However, the combined model of a mixture of CpGs has rarely been evaluated. In the present study, we aimed to develop and validate a CpG-based signature model for HCC patient prognosis. Methods. Data from methylation profiling of GSE73003, GSE37988, and GSE57958 from the Gene Expression Omnibus (GEO) database and 371 HCC patients from the Cancer Genome Atlas (TCGA) were downloaded. The 371 HCC patients were randomly divided into a development cohort (N = 263) and a validation cohort (N = 108). Two algorithms, least absolute shrinkage and selection operator (LASSO) and robust likelihood-based survival analysis, were used to select the most significant CpGs associated with overall survival (OS) time and were used to develop and validate a methylation-based signature (MSH) for HCC patient prognosis. In addition, the prognostic efficacy of the MSH was compared with that of AJCC TNM classification and other CpG-based MSHs from TCGA. Finally, a nomogram incorporating the MSH and clinicopathologic factors was also developed. Results. Fourteen differential CpGs associated with OS were identified in HCC patients. The MSH, based on these 14 differential CpGs, could effectively divide HCC patients into two distinct subgroups with high risk or low risk of death (P<0.0001) in the development cohort (26.35 vs 83.18 months, HR = 3.83, 95% CI: 2.56–5.90, P<0.0001) and in the validation cohort (40.37 vs 107.03 months, HR = 2.23, 95% CI: 1.22–4.17, P=0.01). Univariate analysis showed that the MSH was significantly associated with OS, and the multivariate analysis also showed that the MSH was an independent prognostic factor for the OS of HCC patients in the two cohorts. In addition, stratified survival analysis indicated that the MSH still exhibited good prognostic value in different subgroups classified by AFP, cirrhosis, Child-Pugh A, tumor histologic grade, and AJCC stage. Moreover, time-dependent ROC analysis showed better performance of the MSH in predicting 3-year and 5-year survival of HCC patients than of AJCC stage and other CpG-based signatures from TCGA. The MSH-based nomogram also performed well in predicting 1-year, 3-year, and 5-year OS (C-index: 0.709). Conclusion. The 14-CpG-based signature is significantly associated with OS and may be used as a novel prognostic biomarker for HCC patients.

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