Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa-2a combination therapy for chronic hepatitis B.

BACKGROUND: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy. AIM: To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks. METHODS: A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 µg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72. RESULTS: Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72. CONCLUSIONS: HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.

Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohn's and colitis epidemiology study.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are becoming more common in Asia, but epidemiologic data are lacking. The Asia-Pacific Crohn's and Colitis Epidemiology Study aimed to determine the incidence and phenotype of IBD in 8 countries across Asia and in Australia. METHODS: We performed a prospective, population-based study of IBD incidence in predefined catchment areas, collecting data for 1 year, starting on April 1, 2011. New cases were ascertained from multiple overlapping sources and entered into a Web-based database. Cases were confirmed using standard criteria. Local endoscopy, pathology, and pharmacy records were searched to ensure completeness of case capture. RESULTS: We identified 419 new cases of IBD (232 of ulcerative colitis [UC], 166 of Crohn's disease [CD], and 21 IBD-undetermined). The crude annual overall incidence values per 100,000 individuals were 1.37 for IBD in Asia (95% confidence interval: 1.25-1.51; 0.76 for UC, 0.54 for CD, and 0.07 for IBD-undetermined) and 23.67 in Australia (95% confidence interval: 18.46-29.85; 7.33 for UC, 14.00 for CD, and 2.33 for IBD-undetermined). China had the highest incidence of IBD in Asia (3.44 per 100,000 individuals). The ratios of UC to CD were 2.0 in Asia and 0.5 in Australia. Median time from symptom onset to diagnosis was 5.5 months (interquartile range, 1.4-15 months). Complicated CD (stricturing, penetrating, or perianal disease) was more common in Asia than Australia (52% vs 24%; P = .001), and a family history of IBD was less common in Asia (3% vs 17%; P < .001). CONCLUSIONS: We performed a large-scale population-based study and found that although the incidence of IBD varies throughout Asia, it is still lower than in the West. IBD can be as severe or more severe in Asia than in the West. The emergence of IBD in Asia will result in the need for specific health care resources, and offers a unique opportunity to study etiologic factors in developing nations.

Improved colonoscopy success rate with a distally attached mucosectomy cap.

BACKGROUND AND STUDY AIMS: Although colonoscopy is a well-established procedure, various technical difficulties may cause failure. This report describes experience with cap-assisted colonoscopy (CAC), a technique in which a mucosectomy cap is attached to the end of colonoscope in order to improve the success rate. PATIENTS AND METHODS: From January 2003 to May 2005, CAC was used in consecutive patients with difficult colonoscopy procedures, which were defined firstly as failure to pass through the sigmoid colon after 20 min of examination, or secondly as failure to reach the cecum at the end of the procedure. Patients with prior colonic surgery, poor bowel preparation, distal colonic stricture, or obstructing tumors were excluded. The results with the CAC method were reviewed retrospectively. RESULTS: A total of 100 patients met the criteria for difficult colonoscopy during the study period. When CAC was used to repeat the procedure, cecal and terminal ileal intubation could then be achieved in 94 and 70 patients, respectively. In the remaining six patients in whom cecal intubation failed, one failure was due to a tumor obstruction at the splenic flexure. CONCLUSIONS: CAC can be used as a rescue method to improve the success rate of colonoscopy when failure is encountered.

Optimizing the tensile properties of polyvinyl alcohol hydrogel for the construction of a bioprosthetic heart valve stent.

Although bioprosthetic heart valves offer the benefits of a natural opening and closing, better hemodynamics, and avoidance of life-long anticoagulant therapy, they nevertheless tend to fail in 10-15 years from tears and calcification. Several authors, including the present ones, have identified the rigid stent as a factor contributing to these failures. The ultimate solution is an artificial heart valve that has mechanical properties that allow it to move in conformity with the aortic root during the cardiac cycle, has superior hemodynamics, is nonthrombogenic, will last more than 20 years, and mitigates the need for anticoagulants. We have identified a polymer, polyvinyl alcohol (PVA) hydrogel, that has mechanical properties similar to soft tissue. The purpose of this research is to match the tensile properties of PVA to the porcine aortic root and to fabricate a stent prototype for a bioprosthetic heart valve with the use of the PVA hydrogel. Specimens of 15% w/w PVA were prepared by processing through 1-6 cycles of freezing (-20 degrees C) at 0.2 degrees C/min freeze rate and thawing (+20 degrees C) at different thawing rates (0.2 degrees C/min and 1 degrees C/min), for different holding times (1 and 6 h) at -20 degrees C. Subsequently tensile tests and stress-relaxation tests were conducted on the specimens. The different holding times at -20 degrees C demonstrated no difference in the result. The slower thawing rate improved the tensile properties but did not produce significant changes on the stress-relaxation properties. The nonlinear stress-strain curve for the PVA after the fourth freeze-thaw cycle matched the porcine aortic root within the physiological pressure range. The stress-relaxation curve for PVA also approximated the shape of the aortic root. The complex geometry of an artificial heart valve stent was successfully injection molded. These results, in combination with other preliminary findings for biocompatibility and fatigue behavior, suggest that PVA hydrogel is a promising biomaterial for implants, catheters, and artificial skin.

The pericardial bioprosthesis: altered tissue shear properties following glutaraldehyde fixation.

BACKGROUND AND AIM OF THE STUDY: Glutaraldehyde-fixed bovine pericardial tissue used in the construction of valvular bioprostheses undergoes repeated bending stress during the cardiac cycle. To bend smoothly, internal tissue shearing is required. The effect of glutaraldehyde fixation on internal shear properties of this material was examined. METHODS: Pericardium from each of 12 bovine hearts was cut into two pieces; one piece was retained as fresh tissue, the other was glutaraldehyde-fixed. Circular samples were then mounted and installed in a shear testing apparatus. For each sample, the shear stress versus shear strain characteristics were measured in circumferential and radial directions at strain rates of 1.0, 0.1 and 0.02 s(-1) while immersed in a 20 degrees C bath; similar measurements were made on six fresh and six fixed samples at 37 degrees C. In addition, the stress relaxation properties were measured by holding the tissue at maximum shear for 100 s after each of the three shear deformations, and recording force generated with time. RESULTS: The shear stress-strain test on fresh tissue (n = 12) showed non-linear behavior at the three shear rates. The shear modulus for fresh tissue increased from <1.0 kPa to 5 kPa at a shear strain approaching 1.0, and results were identical in radial or circumferential directions. For glutaraldehyde-fixed pericardium (n = 12), shear modulus increased promptly to 15-20 kPa at a strain of 0.2, and did not vary with strain rate. Shear relaxation was similar in fresh and fixed tissue. CONCLUSION: Fresh pericardium sheared easily at low shear stresses, with minimal resistance developing until the shear strain exceeded 0.5, while glutaraldehyde-fixed tissue displayed a marked resistance to shearing, with an immediate rise in shear stress at low strain. No differences were detected in shear properties between radial and circumferential directions. Such marked tissue stiffening may be a factor in collagen fiber disruption, leading to bioprosthetic heart valve failure.