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Anemia is associated with severe outcomes in adult community-acquired pneumonia (CAP), but few studies investigated its association with pediatric CAP. Hence, we tried to delineate the association of anemia with the clinical outcomes of CAP in children.This retrospective cohort study was conducted from 2010 to 2019 in a medical center. Inpatients aged 6 months to 17 years who were diagnosed with CAP and without major underlying diseases were included. The subjects' clinical data within 24 h of admission and clinical outcomes were collected. We accessed the rates of adverse outcomes and the adjusted odds ratios (ORs) of these outcomes between anemic and nonanemic patients, as well as among patients with different types of anemia.In this study of 3601 patients, the prevalence of anemia was 11.6% (418/3601). Anemic patients had higher rates of intensive care (16.8% vs. 3.6%; p 0.001), endotracheal intubation (11.0% vs. 1.3%; p 0.001), and empyema (8.6% vs. 0.6%; p 0.001) than nonanemic patients. In addition, anemia was independently associated with intensive care (adjusted OR, 3.00; 95% confidence interval [CI], 2.03-4.42), endotracheal intubation (adjusted OR, 3.79; 95% CI, 2.17-6.63), and empyema (adjusted OR, 4.72; 95% CI, 2.30-9.69). Iron-deficiency anemia (IDA) and normocytic anemia were associated with these adverse outcomes but not with anemia due to thalassemia trait.Anemia is a biomarker associated with poor outcomes in pediatric CAP, and patients with IDA or normocytic anemia should be carefully monitored and managed since they may have higher disease severity.

Hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), Epstein-Barr virus (EBV), human T-cell lymphotropic virus type 1 (HTLV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCV) contribute to about 10-15% global burden of human cancers. Conventional chemotherapy or molecular target therapies have been used to treat virus-associated cancers. However, a more proactive approach would be the use of antiviral treatment to suppress or eliminate viral infections to prevent the occurrence of cancer in the first place. Antiviral treatments against chronic HBV and HCV infection have achieved this goal, with significant reduction in the incidence of hepatocellular carcinoma in treated patients. Antiviral treatments for EBV, KSHV, and HTLV-1 had limited success in treating refractory EBV-associated lymphoma and post-transplant lymphoproliferative disorder, KSHV-associated Kaposi's sarcoma in AIDS patients, and HTLV-1-associated acute, chronic, and smoldering subtypes of adult T-cell lymphoma, respectively. Therapeutic HPV vaccine and RNA interference-based therapies for treating HPV-associated infection or cervical cancers also showed some encouraging results. Taken together, antiviral therapies have yielded promising results in cancer prevention and treatment. More large-scale studies in a real-world setting are necessary to confirm the efficacy of antiviral therapy. Further investigation for more effective and convenient antiviral regimens warrants more attention.

Background Enterovirus D68 (EV-D68) was discovered in 1962 and has unique characteristics compared to the characteristics of other enteroviruses. There were few documented cases before the epidemic in the United States in 2014. The Taiwan Centers for Diseases Control also confirmed that EV-D68 has been endemic, and some cases of acute flaccid myelitis were reported in Taiwan. To understand the current EV-D68 serostatus, we performed an EV-D68 seroepidemiology study in Taiwan in 2017. Methods After informed consent was obtained, we enrolled preschool children, 6- to 15-year-old students and 16- to 49-year-old people. The participants underwent a questionnaire investigation and blood sampling to measure the EV-D68 neutralization antibody. Results In total, 920 subjects were enrolled from the northern, central, southern and eastern parts of Taiwan with a male-to-female ratio of 1.03. The EV-D68 seropositive rate was 32% (26/82) in infants, 18% (27/153) in 1-year-old children, 43% (36/83) in 2-year-old children, 60% (94/156) in 3- to 5-year-old children, 89% (108/122) in 6- to 11-year-old primary school students, 98% (118/121) in 12- to 15-year-old high school students, 100% (122/122) in 16- to 49-year-old women and 100% (81/81) in 16- to 49-year-old males in 2017. Among preschool children, EV-D68 seropositivity was related to age (p for trend

Background During recent 20 years, enterovirus 71 (EV71) has emerged as a major concern among children, particularly in the Asia-Pacific region. To understand current EV71 serostatus, to find risk factors associated with EV71 infection and to establish future EV71 vaccine policy, we performed a seroepidemiology study in Taiwan in 2017. Methods After informed consent was obtained, we enrolled preschool children, 6–15-year-old students, 16–50-year-old people. They received a questionnaire and a blood sample was collected to measure the EV71 neutralization antibody. Results Altogether, 920 subjects were enrolled with a male-to-female ratio of 1.03. The EV71 seropositive rate was 10% (8/82) in infants, 4% (6/153) in 1-year-old children, 8% (7/83) in 2-year-old children, 8% (13/156) in 3–5-year-old children, 31% (38/122) in 6–11-year-old primary school students, 45% (54/121) in 12–15-year-old high school students and 75% (152/203) in 16-50-year-old people. Risk factors associated with EV71 seropositivity in preschool children were female gender, having siblings, more siblings, and contact with herpangina or hand-foot-and-mouth disease. The risk factor with EV71 seropositivity in 16–50-year-old people was having children in their families in addition to older age (p

Background Glutamic acid dehydrogenase 1 (GAD1) serves as the rate-limiting enzyme for synthesizing GABA, and is reported to be associated with several psychiatric disorders. The present study examined the effects of GAD1 genetic variants on bipolar disorder (BD) and its subtypes. Moreover, we investigated functional interactions between genetic variants and miRNAs via algorithm prediction and experimental validation. Methods A case-control study was conducted with 280 BD patients and 200 healthy controls. Eight tag SNPs in GAD1 were genotyped. For associated markers, we performed in silico prediction for their potential functions through SNP-miRNA interactions by establishing a scoring system to combine information from several miRNA predictive algorithms. We then tested allelic expression differences using Dual-Glo luciferase reporter assays for the selected SNP-miRNA pair. Lastly, we examined the associations of the GAD1 gene and BD in two additional independent datasets with a few thousand samples for replication. Results Marker rs3749034 was associated with BD, in particular the BD-II subtype. According to our scoring system, several candidate miRNAs were predicted to interact with rs3749034, and hsa-miR-504 had the highest score. Findings from an in vitro experiment revealed a non-statistically significant trend for lower gene expression level with the A allele of rs3749034 compared with the G allele. The association between rs3749034 and BD was not replicated in either of the independent datasets. Instead, other rarer genetic variants in GAD1 showed suggestive signals (e.g. rs575441409, p-value = 3.8*10 −4 , D′ = 1 with rs3749034) with BD in the Taiwanese dataset. Limitations The present study considered common genetic variants only. In addition, we only used a 293 T cell-line in conducting luciferase reporter assays, as no primary cell-lines from patient samples were available to differentiate the effects between BD subtypes. Conclusions Our results demonstrate a weak effect of the GAD1 gene on the risk of bipolar illness, and the associated marker might represent a proxy for real signals of rare variants.

A region on chromosome 4q25 has recently been highlighted as linked to hepatocellular carcinoma (HCC). In this study, we performed a family-based association analysis with 67 single-nucleotide polymorphisms (SNPs) to map this linkage region in 240 families with HCC, 212 (88.3%) of which were ascertained through hepatitis B virus surface antigen (HBsAg)-positive index cases. Individual SNP analysis with correction for multiple testing identified 10 SNPs in two correlated haplotype blocks, located in or around the 3'-phosphoadenosine 5'-phosphosulfate synthetase-1 (PAPSS1) gene (all P-values:0.0075). Our linkage data and GIST (Genotype identity-by-descent sharing test) indicate that 6 of these 10 SNPs contributed to the linkage signal. The haplotype block of the strongest association with HCC extended from the intron 5 to the 3'-flanking region of PAPSS1; multiple consecutive three-SNP haplotypes in this region were significant. The most significant haplotype showed odd ratios of 3.41 (95% confidence interval (CI)=1.36-8.53) for homozygous individuals in a case-unaffected sibling analysis. This haplotype also revealed an association with elevated serum alpha-fetoprotein and with poor survival in familial cases and an independent series of HBsAg-positive cases with small tumor present at the time of hospital admission. These results implicate PAPSS1 as a candidate HCC-susceptibility gene in hepatitis B carriers.

Background: Although chronic infection with hepatitis B virus (HBV) has been established as a cause of hepatocellular carcinoma (HCC), the roles of viral load and HBV genotype remain unclear. Methods: From 1988 through 1992, baseline blood samples were collected from 4841 Taiwanese men who were HBV carriers but had not been diagnosed with HCC. We used real-time polymerase chain reaction assays of plasma DNA samples to quantify HBV DNA levels (a measure of viral load) and determine HBV genotypes for 154 case patients who were diagnosed with HCC during 14 years of follow-up and 316 control subjects. Unconditional logistic regression was used to assess odds ratios (ORs) of HCC for HBV-related factors. All statistical tests were two-sided. Results: The risk of HCC increased with increasing HBV viral load (adjusted OR for the highest versus the lowest quintile of HBV DNA copies/mL = 7.26, 95% confidence interval [CI] = 3.54 to 14.89; P trend

Hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), and Epstein-Barr virus (EBV) contribute to about 10-15 % global burden of human cancers. Conventional chemotherapy or molecular target therapies have been used to treat virus-associated cancers. However, a more proactive approach would be the use of antiviral treatment to suppress or eliminate viral infections to prevent the occurrence of cancer in the first place. Antiviral treatments against chronic HBV and HCV infections have achieved this goal, with significant reduction in the incidence of hepatocellular carcinoma in treated patients. Antiviral treatments for EBV, Kaposi's sarcoma-associated herpesvirus (KSHV), and human T-cell lymphotropic virus type 1 (HTLV-1) had limited success in treating refractory EBV-associated lymphoma and post-transplant lymphoproliferative disorder, KSHV-associated Kaposi's sarcoma in AIDS patients, and HTLV-1-associated acute, chronic, and smoldering subtypes of adult T-cell lymphoma, respectively. Therapeutic HPV vaccine and RNA-interference-based therapies for treating HPV-associated cervical cancers also showed some encouraging results. Taken together, antiviral therapies have yielded promising results in cancer prevention and treatment. More large-scale studies are necessary to confirm the efficacy of antiviral therapy. Further investigation for more effective and convenient antiviral regimens warrants more attention.

Prognosis of hepatocellular carcinoma (HCC) is generally poor. The role of modifiable lifestyle factors on HCC survival has been less studied. To examine whether prediagnosis smoking and alcohol affected HCC survival stratified by viral etiology, we conducted a prospective cohort study of 2,273 (1990 with viral hepatitis and 283 without) incident HCC cases aged 20-75 years who were enrolled between 1997 and 2004 from a Taiwanese multicenter study, and followed up through 2007. Information on habitual smoking and alcohol consumption was obtained at baseline through personal interview. After follow-up to a maximum of 10 years, 1,757 participants died and 1,488 (84.7%) were attributed to HCC. Prediagnosis smoking and alcohol worsened prognosis independent of each other and clinical predictors. The effects of both risky behaviors were limited to viral hepatitis-related HCC and more profound among those with early-stage HCC. Risk for HCC-specific mortality increased with increasing pack-years smoked and ethanol intake (all p < 0.001 for trend), with an additive effect shown for the two habits [hazard ratio (HR) for alcohol ≥ 46.2 g/day and ≥ 10 pack-years = 1.72, 95% confidence interval (CI) = 1.45-2.05]. For either habit, cessation reduced HCC-specific mortality, but a significant mortality benefit occurred 10 years after abstinence (quitting smoking ≥ 10 years vs. continuing smokers: HR = 0.77, 95% CI = 0.61-0.97; quitting drinking ≥ 10 years vs. continuing drinkers: HR = 0.74, 95% CI = 0.56-0.98). In conclusion, among patients with viral hepatitis-related HCC, prediagnosis smoking and alcohol have a deleterious effect on HCC survival. Quitting smoking or drinking alcohol could reduce the excess risk, but only after a long interval of cessation.

High viraemia of hepatitis B virus (HBV) influences all phases in the development of hepatocellular carcinoma (HCC). This study was designed to estimate the overall contribution of host genetics to HBV viraemia, and investigate the influence of common single-nucleotide polymorphisms (SNPs) in the interferon γ (IFNγ) signalling pathway, which is pivotal in the non-cytolytic clearance of HBV.We first determined familial correlations and heritability (ie, proportion of phenotypic variation that is attributable to additive genetic factors) for HBV viraemia using 280 HCC families, including 766 adult HBV carriers. Then family-based association analysis was conducted for viraemia with a panel of 40 SNPs across ten IFNγ-related genes. For replication, seven tagging SNPs in identified candidate regions were also tested in a further 1011 unrelated individuals with longitudinal data on HBV viraemia over 16 years.After adjustment for HBV genotype and sex, significant correlations for viraemia were detected among both siblings and mother-child pairs. Heritability accounted for approximately 30% (p0.0002) of the variance of viral load, whereas HBV genotype and sex together explained less than 3%. Heritability estimates increased up to 74.0% after further exclusion of subjects with episodes of liver biochemical abnormalities. Our initial family-based association analysis identified two SNPs (rs2284553 (intronic SNP) and rs9808753 (Q64R)) on the IFNγ receptor 2 (IFNGR2) gene that were robustly associated with viraemia after multitest correction (all p0.02). The SNPs were also associated with the longitudinal levels of viraemia and the persistence of a high viraemia of ≥4.39 log copies/ml (all p0.0001) in unrelated individuals.HBV viraemia appears to have substantial heritability. Polymorphisms in the IFNGR2 gene appear to be associated with the variability of viraemia.

Purpose To determine prospectively whether body-mass index (BMI) is associated with liver-related morbidity and mortality among male hepatitis B virus (HBV) carriers. Patients and Methods We performed a prospective study of 2,903 male HBV surface antigen–positive government employees who were free of cancer at enrollment between 1989 and 1992. Main outcome measures included ultrasonography, biochemical tests, incident hepatocellular carcinoma (HCC), and liver-related death. Results During mean follow-up of 14.7 years, 134 developed HCC and 92 died as a result of liver-related causes. In Cox proportional hazards models adjusting for age, number of visits, diabetes, and use of alcohol and tobacco, the hazard ratios for incident HCC were 1.48 (95% CI, 1.04 to 2.12) in overweight men (BMI between 25.0 and 29.9 kg/m2) and 1.96 (95% CI, 0.72 to 5.38) in obese men (BMI ≥ 30.0 kg/m2), compared with normal-weight men (BMI between 18.5 and 24.9 kg/m2). Liver-related mortality had adjusted hazard ratios of 1.74 (95% CI, 1.15 to 2.65) in overweight men and 1.50 (95% CI, 0.36 to 6.19) in obese men. Excess BMI was also associated with the occurrence of fatty liver and cirrhosis detected by ultrasonography, as well as elevated ALT and γ-glutamyltransferase (GGT) activity during follow-up. The association of BMI with GGT was stronger than with ALT, and elevated GGT activity and cirrhosis were the strongest predictors for incident HCC and liver-related death. Conclusion This longitudinal cohort study indicates that excess body weight is involved in the transition from healthy HBV carrier state to HCC and liver-related death among men.

Little is known about the longitudinal course of hepatitis B virus (HBV) load and its relationship with the development of hepatocellular carcinoma (HCC). We conducted a case-cohort study nested within a cohort of 2874 HBV surface antigen-positive male Taiwanese government employees aged 30 years or older. HBV genotype and DNA levels (i.e. viral load) were tested using polymerase chain reaction-based assays on plasma samples from 112 cases and 1031 non-cases. Prediagnostic plasma levels of HBV DNA were measured in multiple samples collected from each man (total 7706 samples), taken over periods of up to 16 years before diagnosis. Baseline viral load influenced HBV genotype-specific HCC risks and predicted the persistence of high viral load (/=4.39 log copies/ml) that can cause HCC. Moderate to high tracking of viral load was observed within 9 years. Hepatitis B e antigen (P0.0001), genotype C HBV infection (P = 0.0369) and longitudinal alanine aminotransferase (ALT) elevation (defined as ALT abnormality in/=50% of the visits) (P = 0.0005) were positively related to longer duration of persistence for high viral load. After multivariate adjustment, HBV genotype C [odds ratio (OR) = 5.97, 95% confidence interval (CI) = 3.44-10.34], high viral load detected at/=50% of the visits (compared with sustained low viral load: OR = 5.04, 95% CI = 2.31-11.00) and longitudinal ALT elevation (compared with sustained normal ALT levels: OR = 2.84, 95% CI = 1.46-5.51) accounted for 43.5, 57.2 and 24.9% of HCCs, respectively. The results suggest that maintenance of viral load4.39 log copies/ml was associated with sustained normalization of ALT levels and decreased risk of HCC.

Chromosome 4q is one of the most common regions with a high frequency of allelic loss in hepatocellular carcinoma (HCC). To identify the HCC-susceptibility locus on chromosome 4q, we have performed linkage and family-based association analyses on Chinese families with HCC from Taiwan, where hepatitis B is hyperendemic. Using 77 microsatellite markers spanning chromosome 4q on 52 multiplex families, we found suggestive evidence of linkage to 4q22.3-28.1 with a maximum two-point heterogeneity LOD (HLOD) score of 2.55 at marker D4S3240 on chromosome 4q25. Multipoint analyses with microsatellite markers in the region 4q22.3-28.1 resulted in a maximum HLOD score of 3.12 and a maximum nonparametric linkage (NPL) Z score of 1.98 (pointwise P=0.0080; region-wide empirical P=0.021) for D4S3240. The evidence for linkage to D4S3240 was seen mostly in a subset of 28 families lacking affected parents, which showed multipoint HLOD and NPL scores of 3.25 and 2.79 (pointwise P=0.0028; region-wide empirical P=0.008), respectively. Family-based association analyses of the 77 microsatellite markers in 191 families (53 multiplex plus 138 singleton families) using the pedigree disequilibrium test provide further support for observed linkage. Additional genotyping in the 52 multiplex families informative for linkage analyses was performed for 29 single-nucleotide polymorphisms around D4S3240. A common haplotype (at markers rs7442180 and rs221330) positioned approximately 873 kb away from D4S3240 was associated with HCC, with P=0.0074.

The purpose of this study was to estimate both cross-sectional sibling recurrence risk ratio (λ s ) and lifetime λ s for the metabolic syndrome and its individual components over time among sibships in the prospectively followed-up cohorts provided by the Genetic Analysis Workshop 13. Five measures included in the operational criteria of the metabolic syndrome by the Adult Treatment Panel III were examined. A method for estimating sibling recurrence risk with correction for complete ascertainment was used to estimate the numerator, and the prevalence in the whole cohort was used as the denominator of λ s . Considerable variability in the λ s was found in terms of different time-points for the cross-sectional definition, the times of fulfilling the criterion for lifetime definition, and different components. Obesity and hyperglycemia had the highest cross-sectional λ s of the five components. Both components also had the largest slopes in the linear trend of the lifetime λ s . However, the magnitudes of the lifetime λ s were similar to that of the mean cross-sectional λ s , which were