Addition of Immunosuppressive Treatment to Hemoperfusion Is Associated with Improved Survival after Paraquat Poisoning: A Nationwide Study

Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001). The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001). Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001). Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.     

The Prevalence and Risk Factors for Gallstone Disease in Taiwanese Vegetarians

Introduction

Gallstone disease (GSD) and its complications are major public health issues globally. Although many community-based studies had addressed the risk factors for GSD, little is known about GSD prevalence and risk factors among Taiwanese vegetarians.

Methods

This study included 1721 vegetarians who completed a questionnaire detailing their demographics, medical history, and life-styles. GSD was ascertained by ultrasonography or surgical history of cholecystectomy for GSD. The predictive probability of GSD for male and female vegetarians was estimated from the fitted model.

Results

The prevalence of GSD was 8.2% for both male and female vegetarians. The risk of GSD is similar in men and women across all age groups, and increases steadily with increasing age. For male vegetarians, age (OR: 1.04; 95% CI: 1.00–1.08) and serum total bilirubin level (OR: 2.35; 95% CI: 1.31–4.22) predict risk for GSD. For female vegetarians, age (OR: 1.03; 95% CI: 1.01–1.05), BMI (OR: 1.07; 95% CI: 1.01–1.13), and alcohol consumption (OR: 7.85; 95% CI: 1.83–33.73) are associated with GSD. GSD is not associated with type of vegetarian diet, duration of vegetarianism, low education level, physical inactivity, diabetes, coronary artery disease, cerebral vascular accident, chronic renal failure, hepatitis C virus infection, and lipid abnormalities. GSD is also not associated with age at menarche, postmenopausal status, and multiparity in female vegetarians.

Conclusions

Risk factors useful for predicting GSD in vegetarians are (1) age and total bilirubin level in men, and (2) age, BMI, and alcohol consumption in women. Many previously identified risk factors for general population does not seem to apply to Taiwanese vegetarians.     

Mutagenesis study of rice nonspecific lipid transfer protein 2 reveals residues that contribute to structure and ligand binding

Plant nonspecific lipid transfer protein 2 (nsLTP2) is a small (7 kDa) protein that binds lipid-like ligands. An inner hydrophobic cavity surrounded by alpha-helices is the defining structural feature of nsLTP2. Although nsLTP2 structures have been reported earlier, the detailed mechanisms of ligand binding and lipid transfer remain unclear. In this study, we used site-directed mutagenesis to determine the role of various hydrophobic residues (L8, I15, F36, F39, Y45, Y48, and V49) in the structure, stability, ligand binding, and lipid transfer activity of rice nsLTP2. Three single mutations (L8A, F36A, and V49A) drastically alter the native tertiary structure and perturb ligand binding and lipid transfer activity. Therefore, these three residues are structurally important. The Y45A mutant, however, retains a native-like structure but has decreased lipid binding affinity and lipid transfer activity, implying that this aromatic residue is critical for these biological functions. The mutants, I15A and Y48A, exhibit quite different ligand binding affinities. Y48 is involved in planar sterol binding but not linear lysophospholipid association. As for I15A, it had the highest dehydroergosterol binding affinity in spite of the lower lipid binding and transfer abilities. Our results suggest that the long alkyl side chain of I15 would restrict the flexibility of loop I (G13-A19) for sterol entry. Finally, F39A can markedly increase the exposed hydrophobic surface to maintain its transfer efficiency despite reduced ligand binding affinity. These findings suggest that the residues forming the hydrophobic cavity play various important roles in the structure and function of rice nsLTP2.     

Increased Risk of Urinary Tract Cancer in ESRD Patients Associated with Usage of Chinese Herbal Products Suspected of Containing Aristolochic Acid

Introduction

Both end-stage renal disease (ESRD) and urothelial cancer (UC) are associated with the consumption of Chinese herbal products containing aristolochic acid (AA) by the general population. The objective of this study was to determine the risk of UC associated with AA-related Chinese herbal products among ESRD patients.

Methods

We conducted a cohort study using the National Health Insurance reimbursement database to enroll all ESRD patients in Taiwan from 1998–2002. Cox regression models were constructed and hazard ratios and confidence intervals were estimated after controlling for potential confounders, including age, sex, residence in region with endemic black foot disease, urinary tract infection, and use of non-steroidal anti-inflammatory drugs and acetaminophen.

Results

A total of 38,995 ESRD patients were included in the final analysis, and 320 patients developed UC after ESRD. Having been prescribed Mu Tong that was adulterated with Guan Mu Tong (Aristolochia manshuriensis) before 2004, or an estimated consumption of more than 1–100 mg of aristolochic acid, were both associated with an increased risk of UC in the multivariable analyses. Analgesic consumption of more than 150 pills was also associated with an increased risk of UC, although there was little correlation between the two risk factors.

Conclusion

Consumption of aristolochic acid-related Chinese herbal products was associated with an increased risk of developing UC in ESRD patients. Regular follow-up screening for UC in ESRD patients who have consumed Chinese herbal products is thus necessary.     

Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study

Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21–1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15–1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27–2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22–2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D’ = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.