Previous controlled trials are inconclusive regarding the efficacy of ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC). One hundred fifty adult patients with PSC were enrolled in a long-term, randomized, double-blind controlled trial of highdose UDCA (28-30 mg/kg/day) versus placebo. Liver biopsy and cholangiography were performed before randomization and after 5 years. The primary outcome measures were development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The study was terminated after 6 years due to futility. At enrollment, the UDCA (n ‫؍‬ 76) and placebo (n ‫؍‬ 74) groups were similar with respect to sex, age, duration of disease, serum aspartate aminotransferase and alkaline phosphatase levels, liver histology, and Mayo risk score. During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group (P < 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre-established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo (P < 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria (P ‫؍‬ 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [P < 0.01]). Conclusion: Long-term, high-dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events. (HEPATOLOGY 2009;50:808-814.)

BACKGROUND:The authors evaluated sarcopenia as a predictor of cancer-specific survival (CSS) and overall survival (OS) among patients with urothelial cancer of the bladder undergoing radical cystectomy (RC). METHODS: The lumbar skeletal muscle index (SMI) of 205 patients treated with RC for urothelial cancer between 2000 and 2007 was measured. Sarcopenia was classified according to international consensus definitions (SMI of < 55 cm 2 /m 2 for men and < 39 cm 2 /m 2 for women). The CSS and OS were estimated using the Kaplan-Meier method and compared with the log-rank test. Variables associated with CSS and all-cause mortality were summarized with hazard ratios (HRs). RESULTS: Of 205 patients, 141 (68.8%) were sarcopenic. Patients with sarcopenia were older, but were otherwise similar to patients without sarcopenia with respect to sex, Charlson comorbidity index, American Society of Anesthesiologists score, Eastern Cooperative Oncology Group performance status, receipt of neoadjuvant chemotherapy, TNM stage of disease, and tumor grade (P >.05 for all). The median follow-up was 6.7 years, during which time 135 patients died, including 91 who died of bladder cancer. Sarcopenic patients had significantly worse 5-year CSS (49% vs 72%; P 5.003) and OS (39% vs 70%; P 5.003) compared with patients without sarcopenia. Moreover, sarcopenia was found to be independently associated with both increased CSS (HR, 2.14; P 5.007) and all-cause mortality (HR, 1.93; P 5.004) on multivariable analysis. CONCLUSIONS: The presence of sarcopenia was found to significantly increase a patient's risk of CSS and all-cause mortality after undergoing RC for bladder cancer.

Background: Functional tricuspid regurgitation (FTR) is common in heart failure with reduced ejection fraction and mostly consequent to pulmonary hypertension. However, the intrinsic clinical implications of FTR are not fully understood. Methods: The cohort of all Mayo Clinic patients from 2003 to 2011 diagnosed with heart failure stage B-C and ejection fraction<50%, with FTR grading and systolic pulmonary artery pressure estimation by Doppler echocardiography was identified and outcomes were analyzed. Patients with pacemakers/defibrillators, organic valve disease, or previous valve surgery were excluded. The primary outcome measure was overall mortality (censored at implantation of a defibrillator, ventricular assist device, or cardiac transplantation), adjusting for clinical and echocardiographic associates with mortality and major comorbidities. Results: Among 13 026 patients meeting inclusion criteria, FTR was detected in 88% (N=11 507: 33% trivial, 32% mild, 17% moderate, and 6% severe), aged 68±14 years, 35% women, ejection fraction 36±10%, systolic pulmonary artery pressure 41±14 mm Hg with 20% atrial fibrillation. Covariates independently associated with FTR included elevated systolic pulmonary artery pressure, older age, female sex, lower ejection fraction, mitral regurgitation, and atrial fibrillation (all P <0.0001). FTR was independently associated with more dyspnea, impaired kidney function, and lower cardiac output ( P <0.003 for all). For long-term outcome, higher FTR degree compared with trivial tricuspid regurgitation was independently associated with higher mortality (adjusted hazard ratios 1.09 [1.01-1.17] for mild FTR, 1.21 [1.11-1.33] for moderate FTR and 1.57 [1.39-1.78] for severe FTR); hence, 5-year survival was substantially lower with increasing severity of functional FTR, 68±1% for trivial FTR, 58±2% for mild FTR, 45±2% for moderate FTR, and 34±4% for severe FTR. Conclusions: In this large cohort of patients with heart failure with reduced ejection fraction, FTR was common and independently associated with pulmonary hypertension, atrial fibrillation, and more severe heart failure presentation. Long-term, higher FTR severity is associated with considerably worse survival, independently of baseline characteristics. Given these untoward outcomes associated with FTR in patients with heart failure with reduced ejection fraction, clinical trials should be directed at testing FTR treatment.

Mayo Clinic Foundation.

No abstract