Hepatobiliary Infection after Transjugular Intrahepatic Portosystemic Shunt Creation in Patients with Prior Biliary Intervention: A Multi-Institution Retrospective Study.

PURPOSE: To estimate the risk of hepatobiliary infection, including endoTIPSitis, liver abscesses, and cholangitis, after transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with prior biliary intervention. MATERIALS AND METHODS: This multi-institution, retrospective study identified 76 patients (n = 48 males; mean age, 54.9 years; mean Model for End-stage Liver Disease [MELD] score, 13.2; n = 45 for ascites and n = 23 for varices; n = 31 with prior liver transplantation) among 2,130 (3.6%) undergoing TIPS creation who had prior biliary intervention (n = 19 bilioenteric anastomoses, n = 35 sphincterotomies, n = 28 internal plastic stent placements, n = 4 internal metal stent placements, and n = 6 percutaneous biliary drain placements). The baseline risk of post-TIPS creation hepatobiliary infection was estimated from a control group of 1,202 TIPS creation procedures in patients without prior biliary intervention. RESULTS: Eleven (14.5%) of 76 patients developed hepatobiliary infection after TIPS creation, including 7 with endoTIPSitis, 4 with hepatic abscesses, and 2 with cholangitis. The 30-day risk of infection was 10.9% (95% confidence interval [CI], 3.5%-17.8%), significantly higher than the 0.4% risk (95% CI, 0.1%-0.8%) observed in patients without prior biliary intervention (hazard ratio [HR], 25.56; 95% CI, 8.36-78.13; P < .001). All types of biliary intervention were associated with increased risk of infection, with bilioenteric anastomoses conferring the highest risk. Paradoxically, among patients with prior biliary intervention, use of postprocedural antibiotic prophylaxis was associated with an increased infection risk (HR, 19.85; 95% CI, 2.44-161.50; P = .005). Microbial culture data showed high rates of Enterococcus, Klebsiella, and Candida species. CONCLUSIONS: Prior biliary intervention was associated with a 10.9% risk of hepatobiliary infection, including endoTIPSitis, liver abscess, and cholangitis, within 30 days after TIPS creation.

Distinct encounter complexes of PAI-1 with plasminogen activators and vitronectin revealed by changes in the conformation and dynamics of the reactive center loop.

UNLABELLED: Plasminogen activator inhibitor-1 (PAI-1) is a biologically important serine protease inhibitor (serpin) that, when overexpressed, is associated with a high risk for cardiovascular disease and cancer metastasis. Several of its ligands, including vitronectin, tissue-type and urokinase-type plasminogen activator (tPA, uPA), affect the fate of PAI-1. Here, we measured changes in the solvent accessibility and dynamics of an important unresolved functional region, the reactive center loop (RCL), upon binding of these ligands. Binding of the catalytically inactive S195A variant of tPA to the RCL causes an increase in fluorescence, indicating greater solvent protection, at its C-terminus, while mobility along the loop remains relatively unchanged. In contrast, a fluorescence increase and large decrease in mobility at the N-terminal RCL is observed upon binding of S195A-uPA to PAI-1. At a site distant from the RCL, binding of vitronectin results in a modest decrease in fluorescence at its proximal end without restricting overall loop dynamics. These results provide the new evidence for ligand effects on RCL conformation and dynamics and differences in the Michaelis complex with plasminogen activators that can be used for the development of more specific inhibitors to PAI-1. This study is also the first to use electron paramagnetic resonance (EPR) spectroscopy to investigate PAI-1 dynamics. SIGNIFICANCE: Balanced blood homeostasis and controlled cell migration requires coordination between serine proteases, serpins, and cofactors. These ligands form noncovalent complexes, which influence the outcome of protease inhibition and associated physiological processes. This study reveals differences in binding via changes in solvent accessibility and dynamics within these complexes that can be exploited to develop more specific drugs in the treatment of diseases associated with unbalanced serpin activity.

A prospective study of platelet function in trauma patients.

BACKGROUND: Exsanguination associated with acute traumatic coagulopathy is a leading cause of death following injury. While platelets occupy a pivotal role in clot formation, clinical research has been scant because of complexities resulting from the need for rapid handling and complex testing of platelet functions. While the thrombin pathway has been proposed as a mediator of platelet dysfunction in trauma, it has not been systematically investigated. The purpose of this study was to evaluate the thrombin pathway in platelet dysfunction. METHODS: Forty trauma patients and 20 noninjured controls were enrolled in the study at a Level I trauma center. Platelet aggregation was tested by light transmission aggregometry with two agonists, adenosine diphosphate (ADP) and thrombin receptor agonist peptide (TRAP). Mean fluorescence intensity and percent positivity of CD62 on ADP-activated platelets were evaluated using flow cytometry. Enzyme-linked immunosorbent assays were performed to evaluate the concentrations of D-dimer, thrombin-antithrombin complex (TAT), and prothrombin fragment 1 + 2 (PF 1 + 2) in each sample. RESULTS: Compared with healthy controls, trauma patients had significantly decreased ADP- and TRAP-mediated platelet aggregation and ADP-mediated CD62 expression. In trauma patients, TRAP-mediated aggregation was inversely proportional to head Abbreviated Injury Scale (AIS) score. Glasgow Coma Scale (GCS) score was directly proportional to TRAP- and ADP-mediated aggregation. When compared with controls, significant differences of D-dimer, TAT, and PF 1 + 2 were found. Measures of shock, including admission blood pressure, pulse, base deficit, and lactate level, did not correlate with platelet dysfunction. CONCLUSION: Trauma patients have significantly lower levels of platelet activation and aggregation compared with healthy controls. Severity of head injury was significantly correlated with platelet dysfunction in a stepwise fashion. Trauma patients also have significantly increased levels of D-dimer, TAT, and PF 1 + 2 when compared with healthy controls. Our data suggest that the thrombin receptor pathway plays an important role in platelet dysfunction in trauma. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.

Effect of Obesity on Outcomes of Forefoot Surgery.

BACKGROUND: Forefoot surgery typically is elective, so it is important to define risk factors to educate patients on potential complications. The purpose of this study was to determine if obesity is an independent risk factor that contributes to increased complication rates after forefoot surgery. METHODS: Through a retrospective review of records, 633 patients were identified who had forefoot surgery at one institution between 2008 and 2010. All patients who currently smoked or smoked in the past were excluded to eliminate a confounding factor, as smoking is known to increase complication rates, leaving 427 patients for inclusion, 299 nonobese (BMI less than 30) and 128 obese (BMI more than 30). Medical records were reviewed for the occurrence of complications, including nonunion, delayed union, delayed wound healing, infection, and persistent pain. RESULTS: The overall complication rate was 9%, with similar rates between obese (10%) and nonobese patients (9%). The only specific complication approaching significance (P = .13) was a higher rate of infection in obese patients (4 % compared to 1%), which could be attributed to the higher percentage of diabetic patients in the obese group. Diabetic patients, regardless of weight, had significantly higher rates of infection (P = .03), with a trend toward higher rates of overall complications and delayed wound healing (P = .08 and P < .06, respectively). CONCLUSION: Obesity was not shown to lead to more frequent complications after forefoot surgery. Diabetes was associated with significantly higher rates of infection, regardless of weight. Though not significant, there was a trend toward higher rates of overall complications and delayed wound healing in diabetic patients as well. LEVEL OF EVIDENCE: Level III, retrospective comparative study.