Efficacy and safety of therapeutic ERCP in patients with cirrhosis: a large multicenter study.

BACKGROUND AND AIMS: Patients with cirrhosis may be less than optimal candidates for ERCP because of underlying ascites, coagulopathy, encephalopathy, and other problems. Although the risks of surgery in patients with cirrhosis are well known, few data are available regarding ERCP in patients with cirrhosis. We performed a retrospective, multicenter study of ERCP in patients with cirrhosis to evaluate outcomes, efficacy, and safety. METHODS: Multicenter retrospective study. RESULTS: A total of 538 ERCP procedures were performed on 328 patients with cirrhosis. A total of 229 patients had Child-Pugh (CP) class A, 229 patients had CP class B, and 80 patients had CP class C. Thrombocytopenia and coagulopathy were corrected before ERCP. The 30-day, procedure-related adverse events included post-ERCP pancreatitis (n = 25, 4.6%: 21 mild, 3 moderate, 1 severe), hemorrhage (n = 6, 1.1%), cholangitis (n = 15, 2.8%), perforation (n = 2, 0.4%), aspiration pneumonia (n = 5, 0.9%), bile leakage (n = 1, 0.2%), cholecystitis (n = 1, 0.2%), and death (n = 1, 0.2%). There was a higher incidence of adverse events in patients with CP class B and C disease when compared with those with CP class A disease (11.4%, 11.3%, and 6.1%, respectively; P = .048). There was no correlation between the risk of significant hemorrhage and the presence of coagulopathy or CP class, even in those who underwent a sphincterotomy. The presence of poorly controlled encephalopathy correlated with a higher overall adverse event rate (P = .003). Sub-analysis revealed that patients without primary sclerosing cholangitis had a significantly higher overall rate of adverse events, pancreatitis, bleeding, and cardiopulmonary adverse events after ERCP when compared with those with primary sclerosing cholangitis. CONCLUSIONS: Our study was performed on a large series of patients with cirrhosis undergoing ERCP. Overall, the adverse events seen in patients with cirrhosis are similar to those seen in the general population of patients undergoing ERCP, although patients with CP classes B and C have higher adverse event rates compared with those with CP class A. Patients with cirrhosis without primary sclerosing cholangitis had significantly greater adverse event rates when compared with patients with primary sclerosing cholangitis.

Design of a heterotetrameric coiled coil.

We have successfully designed a simple peptide sequence that forms highly stable coiled-coil heterotetramers. Our model system is based on the GCN4-pLI parallel coiled-coil tetramer, first described by Kim and coworkers (Harbury et al., Science 1993;262:1401-1407). We introduced glutamates at all of the e and c heptad positions of one sequence (ecE) and lysines at the same positions in a second sequence (ecK). Based on a modeling study, these sidechains are close enough in space to form structure-stabilizing salt bridges. We show that ecE and ecK are highly unstable by themselves but form very stable parallel helical tetramers when mixed, as judged by circular dichroism, analytical ultracentrifugation, and disulfide crosslinking studies. The origin of the difference in stabilities between the homomeric structures and the heteromeric structures comes from a combination of the relief of electrostatic repulsions with concomitant formation of electrostatic attractive interactions based on pH and NaCl screening experiments. We quantify the stability of the heterotetrameric coiled coil from a thermodynamic analysis and compare the finding to other similar coiled-coil systems.