[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.

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.

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.

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.

Computer-aided diagnosis in two-phase 201Tl-SPECT of thoracic lesions.

AIM: The retention index, a traditionally quantitative analysis of two-phase (201)Tl single photon emission computed tomography (SPECT) of the chest, is manually calculated by experienced physicians from comparable 2-D ROI. However, a 3-D ROI would provide more information than a 2-D ROI extracted from a single frame of SPECT. We propose a new diagnostic system, computer-aided diagnosis (CAD), to automatically detect suspicious lesions as 3-D objects on chest (201)Tl-SPECT, and assist the physician in interpreting these images. PATIENTS, METHODS: Seventy patients with thoracic lesions and confirmed diagnoses were enrolled to test this automatic CAD system. The reliability of the CAD system in detecting lesions as 3-D objects was compared to the 2-D ROI of (201)Tl-SPECT found by the manually visualized method. Furthermore, we also proposed a novel index, the retention index using the heart (RIH), to differentiate high retention (slow clearance, increasing target to heart ratio) as a criterion for a malignant lesion, from low retention (faster clearance, small or no increase of the target to heart ratio) for benign lesions. RESULTS: The CAD system can achieve a detection rate of 100% in automatically searching for thoracic lesions in (201)Tl-SPECT. In diagnostic performance, the CAD system with the RIH of comparable 3-D objects has an area under the ROC curve of 0.86, higher than the 0.78 of the traditional RI method (p=0.198). CONCLUSION: The CAD system of two-phase (201)Tl-SPECT is a promising tool for detecting and diagnosing thoracic lesions with a diagnostic accuracy of 0.81.

Ultrasensitive heterogeneous immunoassay using photothermal deflection spectroscopy. 2. Quantitation of ultratrace carcinoembryonic antigen in human sera.

We previously proposed a photothermal immunoassay based on highly sensitive detection by a photothermal beam deflection method using colloidal gold as a labeling material. The assay system was significantly improved in terms of background reduction of ultrasensitive laser spectrometry through the newly designed reaction and separation procedure using microspheres for a solid phase. Highly sensitive laser spectrometric analysis is often susceptible to interference by even a small amount of admixtures. In this subsequent study, we improved our photothermal immunoassay so that it possesses further selectivity, matching that of the highly sensitive photothermal detection method. It was proved that our method could be applied to determine ultratrace quantities of a carcinoembryonic antigen (CEA) in cancer patients' and normal sera. The lower detection limit of CEA was 0.078 ng/mL (9.8 amol, absolute quantity). This is 10 times superior to that of any other immunoassay method and has enough detectability to measure a low level of CEA in healthy individuals. Intraassay coefficient of variation is about 8% at eight different concentrations (n = 6). We assayed 61 serum samples, and there was a good correlation between this method and previously established ELISA. We obtained clearer demarcation of healthy persons and colon cancer patients in terms of the CEA value than was obtained by ELISA. We believe this is the first report in which the laser-based ultrasensitive immunoassay is proved to be applicable to human sera, although the matrix admixtures causing interference in the assay were quite different in each sample serum.

Quantitation of IgE and carcinoembryonic antigen (CEA) by optical beam deflection (OBD) measurement of dot-immunobinding assay patterns visualized by an ELISA technique.

Dot-immunobinding assays of IgE and CEA were performed by a conventional dot-ELISA technique with diaminobenzidine staining, and the quantitative results were compared by densitometry and a new, spectroscopic, optical beam deflection (OBD) method using the same membrane. It was possible with the OBD method to detect quantities of these substances at least ten times smaller than with densitometry. Better intra-assay reproducibility for IgE and CEA measurements was obtained by the OBD method. The measurable ranges of the OBD method was broader than that of densitometry, because dark bands caused OBD in proportion to their color densities. When the dot-immunobinding assay with OBD measurement for CEA was also compared with a microtube ELISA using biotin-avidin conjugates, the sensitivities and reproducibilities of the two methods were found to be similar, with a correlation coefficient of 0.991.