Risk of tuberculosis comparison in new users of antitumour necrosis factor-α and with existing disease-modifying antirheumatic drug therapy.

WHAT IS KNOWN AND OBJECTIVE: Patients with rheumatic disease are at risk for infections. Evaluating antitumour necrosis factor (anti-TNF) drug-associated risk of infections requires justification of baseline risk in the population at high risk of infection. We examined the incidence of active tuberculosis (TB) and its risk factors in patients with rheumatic disease started with anti-TNF-α therapy or with existing disease-modifying antirheumatic drug (DMARD) therapy. METHODS: A retrospective cohort study of anti-TNF-α therapy new users (anti-TNF-α group) and those starting with a DMARD after the failure of at least one other DMARD or who had added to existing DMARD treatment (DMARD group) for rheumatic disease in the largest medical setting in Taiwan from 1 January 2005 through 31 November 2013 was conducted to determine relative risk of TB between patient groups. Patients in the DMARD group were stratified into "mild" and "severe" disease severity as proxies for low and high background risk of infection. RESULTS AND DISCUSSION: A total of 3640 patients were enrolled (anti-TNF: 955; DMARD: 2685). The incidence of TB was 903.9/100 000 patient-years for anti-TNF-α new users and 391.7/100 000 patient-years for DMARD switchers. In Cox regression model, adjusted HR for TB in the anti-TNF-α group was higher than for the entire DMARD group (aHR, 2.41; 95% confidence interval [CI], 1.2-4.85), subgroup with mild disease (2.91; 1.31-6.47) and subgroup with severe disease (1.65; 0.68-4.03). Significant independent risk factors for TB were being male, age ≥60 years, history of respiratory disease, glucocorticoids dose >7.5 mg/d and living in a TB-prevalent region. WHAT IS NEW AND CONCLUSION: Anti-TNF-α therapy was independently associated with increased risk of TB in patients with mild disease, but it was not significantly correlated in patients with severe disease after adjusting for confounders.

Identification of latent biomarkers in hepatocellular carcinoma by ultra-deep whole-transcriptome sequencing.

There is an urgent need to identify biomarkers for hepatocellular carcinoma due to limited treatment options and the poor prognosis of this common lethal disease. Whole-transcriptome shotgun sequencing (RNA-Seq) provides new possibilities for biomarker identification. We sequenced ∼250 million pair-end reads from a pair of adjacent normal and tumor liver samples. With the aid of bioinformatics tools, we determined the transcriptome landscape and sought novel biomarkers by further empirical validations in 55 pairs of adjacent normal and tumor liver samples with various viral statuses such as HBV(+), HCV(+) and HBV(-)HCV(-). We identified a novel gene with coding regions, termed DUNQU1, which has a tissue-specific expression pattern in tumor liver samples of HCV(+) and HBV(-)HCV(-) hepatocellular carcinomas. Overexpression of DUNQU1 in Huh7 cell lines enhances the ability to form colonies in soft agar. Also, we identified three novel differentially-expressed protein-coding genes (ALG1L, SERPINA11 and TMEM82) that lack documented expression profiles in liver cancer and showed that the level of SREPINA11 is correlated with pathology stages. Moreover, we showed that the alternative splicing event of FGFR2 is associated with virus infection, tumor size, cirrhosis and tumor recurrence. The findings indicate that these new markers of hepatocellular carcinoma may be of value in improving prognosis and could have potential as new targets for developing new treatment options.

Strongyloides stercoralis infection in an intestinal transplant recipient.

Strongyloides stercoralis is a helminth in tropical and subtropical areas. It may cause latent infection and progress to Strongyloides hyperinfection syndrome, which is associated with a high mortality rate. Transplant recipients under the treatment of immunosuppressant agents are at risk of severe S. stercoralis infection. According to related literature, most cases of S. stercoralis infection after solid organ transplantation are caused by reactivation of latent infections in the recipients, whereas only a few are acquired from the donors. We report on an intestinal transplant recipient who had S. stercoralis infection diagnosed by a larva of this parasite found in the stool from the ileostomy stoma 1 month after transplantation. The donor was considered the source of the infection because the donor was from an endemic area and had marked eosinophilia, and the recipient had no contact history or clinical manifestations related to the S. stercoralis infection before transplantation. The patient was treated with ivermectin and exhibited no evidence of infection after 7 months.

The use of phenome-wide association studies (PheWAS) for exploration of novel genotype-phenotype relationships and pleiotropy discovery.

The field of phenomics has been investigating network structure among large arrays of phenotypes, and genome-wide association studies (GWAS) have been used to investigate the relationship between genetic variation and single diseases/outcomes. A novel approach has emerged combining both the exploration of phenotypic structure and genotypic variation, known as the phenome-wide association study (PheWAS). The Population Architecture using Genomics and Epidemiology (PAGE) network is a National Human Genome Research Institute (NHGRI)-supported collaboration of four groups accessing eight extensively characterized epidemiologic studies. The primary focus of PAGE is deep characterization of well-replicated GWAS variants and their relationships to various phenotypes and traits in diverse epidemiologic studies that include European Americans, African Americans, Mexican Americans/Hispanics, Asians/Pacific Islanders, and Native Americans. The rich phenotypic resources of PAGE studies provide a unique opportunity for PheWAS as each genotyped variant can be tested for an association with the wide array of phenotypic measurements available within the studies of PAGE, including prevalent and incident status for multiple common clinical conditions and risk factors, as well as clinical parameters and intermediate biomarkers. The results of PheWAS can be used to discover novel relationships between SNPs, phenotypes, and networks of interrelated phenotypes; identify pleiotropy; provide novel mechanistic insights; and foster hypothesis generation. The PAGE network has developed infrastructure to support and perform PheWAS in a high-throughput manner. As implementing the PheWAS approach has presented several challenges, the infrastructure and methodology, as well as insights gained in this project, are presented herein to benefit the larger scientific community.

Using brachial-ankle pulse wave velocity to associate arterial stiffness with cardiovascular risks.

BACKGROUND AND AIMS: This study aimed to elucidate the relationship between brachial-ankle pulse wave velocity (baPWV) and conventional cardiovascular risk factors. METHODS AND RESULTS: A total of 192 subjects with low to intermediate risk was enrolled in a cardiovascular evaluation program. A multiple regression model was built to find significant cardiovascular biomarkers for predicting baPWV. A logistic regression model was developed to associate baPWV and other biomarkers with the risk of cardiac diastolic dysfunction. A total of 123 men (mean age: 52.6+/-12.0) and 69 women (mean age: 51.7+/-10.4) was included. Age, blood pressure, C-reactive protein, serum homocysteine, heart rate, and blood urea nitrogen were positively predictive of increased pulse wave velocity. In turn, baPWV increased the risk (odds ratio: 1.257 for each m/s, 95% CI: 1.105 approximately 1.430, p<0.001) and high-density lipoprotein decreased the risk for cardiac diastolic dysfunction (0.962 for each mg/dl, 95% CI: 0.925 approximately 1.000, p=0.05). The correlation between baPWV and Framingham 10-year risk was moderate (men: r=0.306, p=0.002; women r=0.548, p<0.001). CONCLUSION: The results suggest that baPWV is a composite risk factor for early atherosclerotic change and a predictor for the development of diastolic dysfunction and long-term cardiovascular risk.

Bacteraemia due to ciprofloxacin-resistant Salmonella enterica serotype Choleraesuis in adult patients at a university hospital in Taiwan, 1996-2004.

Eighty-one adult patients with Salmonella enterica serotype Choleraesuis (S. Choleraesuis) bacteraemia treated at a university hospital from 1996 to 2004 were evaluated. Multivariate analysis with a logistic regression model was used to characterize risk factors for primary bacteraemia and mycotic aneurysm and to determine the association of clinical characteristics of patients based on ciprofloxacin susceptibility of the causative organism. The incidence per 100,000 discharges was 0.76 in 1996 and 3.9 in 2004. The overall rate of ciprofloxacin resistance among these isolates was 59% (87 isolates) and the annual rate increased with time from 0% prior to 2000 to 80% in 2004. Among these patients, 48 (59%) had primary bacteraemia and 13 (16%) had secondary bacteraemia with mycotic aneurysm. Seventy (86%) patients had fever at presentation, 22 (27%) developed shock during hospitalization, and eight (10%) died of S. Choleraesuis bacteraemia. Patients with immunocompromised conditions had a higher risk of developing primary bacteraemia (OR 18.442, P < 0.001). Hypertension (OR 15.434, P = 0.002) and male gender (OR 7.422, P = 0.039) were associated with mycotic aneurysm. Patients with mycotic aneurysm were more frequently infected with ciprofloxacin-susceptible isolates (P = 0.028) and ciprofloxacin-susceptible isolates were also more frequently associated with recurrent infection than ciprofloxacin-resistant isolates (P = 0.038). The incidence of S. Choleraesuis bacteraemia has increased in the past 8 years, and this increase is associated with the upsurge of ciprofloxacin-resistant isolates.

Clinical features and predictors for mortality in patients with infective endocarditis at a university hospital in Taiwan from 1995 to 2003.

The clinical features and microbiological characteristics of 315 patients with definite or possible infective endocarditis (IE) from January 1995 to December 2003 were evaluated. There were 187 males and 128 females with a mean age of 51 years (range, 1 month to 92 years). Ninety-three patients (30%) had a diagnosis of valvular heart disease and 24 (8%) had received prosthetic valve replacement. Blood culture was negative in 62 patients (20%). Staphylococci (91 patients, 32%), including methicillin-susceptible Staphylococcus aureus (15%), methicillin-resistant S. aureus (11%), and coagulase-negative staphylococci (6%), were the most commonly encountered pathogens followed by viridans group streptococci (77 patients, 24%). Eight patients (25%) had various neurological, renal, embolic, and cardiac complications. Patients with neurological complications [odds ratio (OR) 8.175, P<0.001], nosocomial IE (OR 6.661, P<0.001), underlying malignancy (OR 4.993, P<0.001), elevated serum creatinine level (OR 3.132, P=0.001), or elevated WBC count (>15000/mm3) (OR 2.537, P=0.007) were at significantly increased risk of mortality. This study found mortality from IE was associated with several factors, among which neurological complications were the most hazardous. Patients with more than one risk factor had poorer prognosis. These results suggest the need for more aggressive management in patients with IE when multiple risk factors for mortality are identified.

Sorption and diffusion behavior of Cs and Sr on Jih-Hsing bentonite.

Sorption and diffusion are important processes for the transport of radionuclides through buffer materials such as bentonite. In this study, the sorption and diffusion behaviors of Cs and Sr on Jih-Hsing bentonite are investigated using batch and through-diffusion techniques. The distribution coefficients (Kds) of Cs and Sr from batch experiments are approximately 1200 ml/g and 800 ml/g, respectively. It is found that the Freundlich isotherm model could fit the sorption isotherm with an equilibrium concentration of 10(-7)-10(-1) N. The calculated retardation factors (Rds) for samples at densities of 1.8 g/cm3, 2.0 g/cm3 and 2.2 g/cm3 are 5685, 7744, and 11000 for Cs, and are 3790, 5162, and 7334 for Sr. For the through-diffusion experiments on the compacted samples with the same densities, the corresponding apparent diffusion coefficients for Cs are (2.83+/-0.75) x 10(-13) m2/s, (1.97+/-0.02) x 10(-13) m2/s, and (1.91+/-0.12) x 10(-13) m2/s, respectively. The corresponding apparent diffusion coefficients for Sr are (1.33+/-0.13) x 10(-13) m2/s, (1.51+/-0.15) x 10(-13) m2/s, and (1.34+/-0.10) x 10(-13) m2/s. The Rds obtained from the diffusion experiments for sample densities of 1.8 g/cm3, 2.0 g/cm3 and 2.2 g/cm3 are 1166+/-355, 2113+/-123, 2796+/-171 for Cs, and 713+/-258, 510+/-68, 846+/-158 for Sr. It appears that the retardation factors obtained from the diffusion experiments are about one order of magnitude lower than those derived from the batch experiments. The discrepancy and the possible explanations are discussed in the paper.