Total bilirubin trend as a predictor of common bile duct stones in acute cholecystitis and symptomatic cholelithiasis.

BACKGROUND: We hypothesized that trends in total bilirubin in the context of cholecystitis and symptomatic cholelithiasis could be used to guide testing for the presence of common bile duct stones (CBDS). METHODS: A review of adult patients with acute cholecystitis or biliary colic with elevated total bilirubin and at least two levels drawn prior to procedural intervention was performed. Trends of total bilirubin and other serum makers were examined to predict the presence of CBDS. RESULTS: The total bilirubin level at presentation, average over 24 h and average over 48 h (3.74 mg/dl vs. 2.29 mg/dl, p = 0.005; 3.72 mg/dl vs. 2.40 mg/dl, p = 0.009; 2.41 mg/dl vs. 1.47 mg/dl, p < 0.001) respectively, were all higher in those with CBDS. However, prediction was not improved by following levels over time. CONCLUSION: Patients presenting with elevated serum bilirubin, should undergo immediate imaging or procedural intervention rather than obtaining follow-up bilirubin levels.

Reduced sox9 function promotes heart valve calcification phenotypes in vivo.

RATIONALE: Calcification of heart valve structures is the most common form of valvular disease and is characterized by the appearance of bone-like phenotypes within affected structures. Despite the clinical significance, the underlying etiology of disease onset and progression is largely unknown and valve replacement remains the most effective treatment. The SRY-related transcription factor Sox9 is expressed in developing and mature heart valves, and its function is required for expression of cartilage-associated proteins, similar to its role in chondrogenesis. In addition to cartilage-associated defects, mice with reduced sox9 function develop skeletal bone prematurely; however, the ability of sox9 deficiency to promote ectopic osteogenic phenotypes in heart valves has not been examined. OBJECTIVE: This study aims to determine the role of Sox9 in maintaining connective tissue homeostasis in mature heart valves using in vivo and in vitro approaches. METHODS AND RESULTS: Using histological and molecular analyses, we report that, from 3 months of age, Sox9(fl/+);Col2a1-cre mice develop calcific lesions in heart valve leaflets associated with increased expression of bone-related genes and activation of inflammation and matrix remodeling processes. Consistently, ectopic calcification is also observed following direct knockdown of Sox9 in heart valves in vitro. Furthermore, we show that retinoic acid treatment in mature heart valves is sufficient to promote calcific processes in vitro, which can be attenuated by Sox9 overexpression. CONCLUSIONS: This study provides insight into the molecular mechanisms of heart valve calcification and identifies reduced Sox9 function as a potential genetic basis for calcific valvular disease.