[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

Research Progress of Metabolomics in Forensic Pathology.

ABSTRACT: Metabolomics is an interdisciplinary subject that rose in the post-genomic era, which focuses on quantitative study of the response of living organisms to outside stimulation and pathophysiological changes, as well as multiple dynamic response of the level of in vivo metabolites caused by genetic mutation. It is extensively used in basic research of system biology, materia medica, clinical medicine, etc. In the forensic field, metabolomics mainly focuses on forensic toxicology, but with the generalization of certain techniques, it's foreseeable that metabolomics has a broad research prospect in forensic pathology. This article summarizes the major analysis techniques and methods of metabolomics, describes the research status of metabolomic techniques in the field of forensic pathology application research, including postmortem interval and death cause. Moreover, this article summarizes and discusses the potential applicable areas, in order to provide reference for relative research and application.

[Research Progress of CircRNA and Its Application Prospect in Forensic Medicine].

Circular RNA （circRNA） is a type of noncoding RNA with tissue specificity and high stability, which forms a closed continuous loop and is abundantly expressed in tissue cells. According to recent research, the regulatory function of circRNA elucidating in the occurrence and development of disease shows a potential for diagnosing clinical disease and revealing disease mechanism. This paper reviews the biological characteristics, analysis methods of circRNA and its research progress in clinical application as biomarker, and outlooks its application in the field of forensic medicine.

Risk of empyema in patients with end-stage renal disease: a nationwide propensity-matched cohort study.

BACKGROUND: Empyema is a rare but important complication among patients with end-stage renal disease (ESRD). However, a nationwide, propensity-matched cohort study has never been performed. METHODS: We conducted a retrospective cohort study using data from the National Health Insurance Research Database of Taiwan. The ESRD group consisted of 82 765 patients diagnosed between 2000 and 2008. The comparison group consisted of individuals without kidney disease selected at a 1:1 ratio matched by propensity score estimated with age, gender, year of diagnosis and comorbidities. The occurrence of empyema was monitored until the end of 2011. The hazard ratios (HRs) of empyema were estimated using the Cox proportional hazards model. RESULTS: The incidence of empyema was 2.76-fold higher in the ESRD group than in the comparison group (23.7 vs. 8.19/10 000 person-years, P <0.001), with an adjusted HR of 3.01 [95% confidence interval (CI) = 2.67-3.39]. There was no difference of the incidence of empyema between hemodialysis (HD) and peritoneal dialysis (PD) (adjusted HR = 0.96, 95% CI = 0.75-1.23). In addition, 30-day mortality rate since empyema diagnosis was significantly higher in ESRD group than the comparison group (15.9% vs. 10.9%), with an adjusted OR of 1.69 (95% CI = 1.17-2.44). CONCLUSION: The risk of empyema was significantly higher in patients with ESRD than in those without kidney disease. The occurrence of empyema was without difference in patients undergoing HD compared to those undergoing PD. The 30-day mortality rate since empyema diagnosis was also significantly higher in patients with ESRD.

Previous history of tuberculosis is associated with rheumatoid arthritis.

BACKGROUND: Previous studies have suggested that mycobacterial infections could trigger autoimmune diseases, including rheumatoid arthritis (RA). OBJECTIVE: To explore the association between previous tuberculosis (TB) and RA. METHODS: We conducted a case-control study using data obtained from the National Health Insurance (NHI) system of Taiwan. We identified 26 535 adults with RA from 2002 to 2011, with the date of diagnosis as the index date. This number was randomly selected and frequency-matched four times by age, sex and the year of index date from among non-RA individuals. Odds ratios (ORs) of RA were calculated for associations with TB. RESULTS: Compared with controls, RA patients had a crude OR of 1.77 for TB (95%CI 1.61-1.94). The strength of the association between RA and TB remained at the same level after controlling for other potential risk factors (adjusted OR 1.73, 95%CI 1.57-1.90), although RA patients tended to have a higher prevalence of hypertension, coronary artery disease and kidney disease. CONCLUSION: TB was much more prevalent in RA patients than in control subjects. Prospective cohort studies are required to establish a causal relationship between previous TB and RA.

Risk of cataract for people with tuberculosis: results from a population-based cohort study.

BACKGROUND: Tuberculosis (TB) is an infectious disease involving multiple organs, including the eyes. We examined the risk of cataract among patients with TB using population data. METHOD: Using data from the National Health Insurance (NHI) system of Taiwan, we established a TB cohort with 6994 patients newly diagnosed between 2000 and 2010. For each TB patient, four subjects without TB were randomly selected for the non-TB cohort, frequency matched by age, sex and diagnosis years. The incidence of cataract was measured by the end of 2011. The hazard ratio (HR) of cataract was estimated using Cox proportional hazards regression analysis. RESULTS: The overall incidence rate of cataract was 21% greater in the TB cohort than in the non-TB cohort (22.9 vs. 18.8/1000 person-years, P < 0.001), with an adjusted HR (aHR) of 1.26 (95%CI 1.16-1.37). Cataract incidence increased with age, and was higher in men than women and much higher for those with comorbidity. The hazard of cataract was higher in the first 6 months after TB diagnosis. CONCLUSION: TB patients are at elevated risk of developing cataract. Although the incidence decreased with time, the aHR remains statistically significant through the follow-up years.

Comparative study of several microinvasive treatments for large hepatocellular carcinoma.

OBJECTIVE: To study the prognosis of large hepatocellular carcinoma after interventional radiology and to compare the efficacy of different microinvasive treatments. PATIENTS AND METHODS: The clinical data of 46 large hepatocellular carcinoma patients confirmed by clinical treatment or pathological examination were retrospectively analyzed. Patients were divided into two groups (TACE+RFA n=23 cases, and Combination group n=23 cases), according to the treatments method. two groups were followed up for 5-48 months. Survival was estimated using the Kaplan-Meier method and the survival curve was compared by log-rank test. RESULTS: Median follow-up time was 33 months in both groups. The median survival time in Combination group (n=41 months) was significantly longer than TACE+RFA group (n=33 months) (p = 0.052). Median progress-free survival (PFS) is 10 months in Combination group and 8 months in TACE+RFA group. The difference was statistically significant (p = 0.023). The tumor inhibition rate was 82.6% and 52.2%, respectively and the difference was statistically significant (p = 0.028). The overall survival rate at l, 2 and 3 years was 100%, 95.7% and 55.8% respectively in Combination group was higher than TACE+RFA group at 91.3%, 55.8% and 38.3% respectively. The difference was not statistically significant. CONCLUSIONS: For large hepatocellular carcinoma, combined method was superior to TACE+RFA and comprehensive treatment can improve the local-control rate.

The association between chronic obstructive pulmonary disease and dementia: a population-based retrospective cohort study.

BACKGROUND AND PURPOSE: Chronic obstructive pulmonary disease (COPD) is frequently associated with various comorbidities. However, the proportion of COPD patients with dementia has not been adequately examined. This retrospective cohort study investigated the association between COPD and dementia by using a nationwide population-based database in Taiwan. METHODS: Data were retrieved from the Taiwanese National Health Insurance Research Database and analyzed using multivariate Cox proportional hazards regression models to assess the effects of COPD on the risk of dementia after adjusting for demographic characteristics and comorbidities. RESULTS: The COPD cohort exhibited a higher prevalence of diabetes, hypertension, coronary artery disease, head injury and depression at baseline than did the non-COPD cohort (P < 0.0001). After adjusting for covariates, the COPD patients exhibited a 1.27-fold higher risk of developing dementia (hazard ratio 1.27, 95% confidence interval 1.20-1.36). The incidence rate was higher in patients with frequent acute exacerbations than in the non-COPD patients regardless of whether a hospital admission or emergency room visit was required (hazard ratio 196.8 vs. 41.7, 95% confidence intervals 145.9-265.5 and 22.3-78.0). CONCLUSION: This study shows that COPD is associated with a subsequent higher risk of dementia after adjusting for comorbidities. Specifically, the association between COPD and dementia is greater in patients with more frequent acute exacerbation events of COPD.

The risk of chronic kidney disease in tuberculosis: a population-based cohort study.

BACKGROUND: The relationship between tuberculosis (TB) and subsequent chronic kidney disease (CKD) remains unclear. Therefore, we examined the risk of CKD among patients with TB in a nationwide study. METHODS: We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan. The cohort included 8735 patients who were newly diagnosed with TB. Patients were recruited between 1998 and 2002, and the date of diagnosis was defined as the index date. Each patient was randomly matched with four people from the general population without TB, according to age, gender and the index year. The occurrence of CKD was followed up until the end of 2011. The relative risks of CKD were estimated using the Cox proportional hazard model after adjusting for age, gender, index year and comorbidities. RESULTS: The overall incidence of CKD was 1.27-fold greater in the TB cohort than in the non-TB cohort. The adjusted hazard ratio (HR) of CKD associated with TB was higher in women (1.72; 95% confidence interval [CI]: 1.33-2.22), those aged <50 years (1.67; 95% CI: 1.15-2.41) and those without comorbidities (1.39; 95% CI: 1.06-1.83). In addition, patients with more comorbidities among hypertension, diabetes and hyperlipidemia have a greater risk of developing CKD in both cohorts, and the adjusted HRs were higher in the TB cohort than in the non-TB cohort. CONCLUSION: TB patients had a significantly higher risk of developing CKD than the general population. The detailed mechanisms need further investigation.

The association between chronic obstructive pulmonary disease and Parkinson's disease: a nationwide population-based retrospective cohort study.

OBJECTIVE: Previous research has shown that patients with chronic obstructive pulmonary disease (COPD) tend to have a higher risk for cognitive impairment and dementia, a neurodegenerative disorder. The goal of this study was to examine what relationship, if any, exists between COPD and Parkinson's disease (PD), which is also a neurodegenerative disorder. METHOD: Our study analyzed medical data from the population of Taiwan from 1998 to 2008, with a follow-up period extending to the end of 2010. We identified patients with COPD by the Taiwan National Health Insurance Research Database (NHIRD). We selected a comparison cohort from the general population that was random frequency-matched by age (in 5-year increments), sex and index year, and further analyzed the risk of PD using Cox's regression model, including sex, age and comorbidities. RESULTS: The study enrolled 20 728 COPD patients (71.1% male, mean age = 68.2 years) and 41 147 controls. The risk of developing PD was 1.37 times greater in patients with COPD compared with patients without COPD after adjusting for age, sex and comorbidities. A significantly increased risk of PD was also found in patients with COPD who had any comorbidity other than diabetes. CONCLUSION: This nationwide retrospective cohort study demonstrates that PD risk is significantly increased in patients with COPD compared with those of the general population.

Increased risk of chronic obstructive pulmonary disease in patients with rheumatoid arthritis: a population-based cohort study.

BACKGROUND: The role of autoimmune pathology in development and progression of chronic obstructive pulmonary disease (COPD) is becoming increasingly popular. Our aim was to assess the association between patients with rheumatoid arthritis (RA) and subsequent COPD risk in a nationwide population. METHOD: We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan. The RA cohort included patients who were newly diagnosed and recruited between 1998 and 2008. Each patient was randomly frequency-matched for age, sex and the year of index date with people without RA from the general population. The newly diagnosed COPD was followed up until the end of 2010. The relative risks of COPD were estimated using Cox proportional hazard models after adjusting for age, sex, index year and comorbidities. RESULT: The overall incidence rate of COPD was 1.74-fold higher in the RA cohort than in the non-RA cohort (5.25 vs. 3.01 per 1000 person-years, 95% confidence interval (CI) = 1.68-1.81). Age-related risk analysis showed an increased incidence of COPD with age in both RA and non-RA cohorts. However, adjusted hazard ratio (HR) maximum was witnessed in the age range of 20-34 years (adjusted HR: 7.67, 95% CI=1.94-30.3), whereas adjusted HR minimum was observed in the oldest age group (>65 years). CONCLUSION: Patients with RA have a significantly higher risk of developing COPD than that of the control population. Further, age-related risk analysis indicated much higher adjusted HR in younger patients although COPD incidence increased with age. It can be hypothesized that in addition to cigarette smoke, RA may be a determining factor for COPD incidence and/or facilitates shortening of the time course for developing COPD. However, further investigation is needed to corroborate this hypothesis.

The risk of asthma in rheumatoid arthritis: a population-based cohort study.

BACKGROUND: Several studies discussed the relations between asthma and rheumatoid arthritis (RA) but the results were controversial. These studies were either questionnaire based or with small study populations. We aimed to examine the risk of asthma among RA patients in a nationwide population. METHODS: We conducted a cohort study using data from the National Health Insurance system of Taiwan. The RA cohort included 27 602 patients who were newly diagnosed and recruited between 1998 and 2008. Each patient was randomly frequency-matched with three people without RA on age group, sex and the year of index date from the general population. The occurrence of asthma was followed up until the end of 2010. The relative risks of asthma were estimated using Cox proportional hazard models after adjusting for age and comorbidities. RESULT: The overall incidence rate of asthma was 2.07-fold greater in the RA cohort than in the non-RA cohort (4.56 vs. 2.22 per 1000 person-years, 95% CI = 1.99-2.15). Stratified analyses by gender, age group and comorbidity revealed that the risk of asthma associated with RA was higher in females (adjusted hazard ratio (HR) = 2.18, 95% CI = 1.97-2.41), individuals younger than 40 years old (adjusted HR = 3.26, 95% CI = 2.09-5.11) and without comorbidity (adjusted HR = 2.17, 95% CI = 1.97-2.39). CONCLUSION: Patients with RA had a significantly higher risk of developing asthma than healthy people in all sex and age subgroups. Stratified analyses indicated that there was a higher risk in women with RA than in men with RA when compared to their counterpart. Similarly, the HR of asthma associated with RA was higher in younger subjects, although the incidence rate increased with age.