Unusual Case of Mirizzi Syndrome Presenting as Painless Jaundice.

BACKGROUND Isolated painless jaundice is an uncommon presenting sign for Mirizzi syndrome, which is typically characterized by symptoms of acute or chronic cholecystitis. We report a rare case of Mirizzi syndrome with an acute onset of painless obstructive jaundice. CASE REPORT A 60-year-old man with an unremarkable prior medical history presented with 1 week of jaundice, dark urine, and acholic stools. His laboratory studies revealed a pattern of cholestasis with marked direct hyperbilirubinemia. Ultrasound and magnetic resonance imaging studies demonstrated intrahepatic ductal dilation and cholelithiasis, including a stone within the cystic duct. Endoscopic retrograde cholangiopancreatography with SpyGlass cholangioscopy confirmed the diagnosis of Mirizzi syndrome. CONCLUSIONS An atypical presentation of Mirizzi syndrome should be suspected in the setting of biliary obstruction without pain. The differential diagnosis is broad and includes choledocholithiasis, ascending cholangitis, and hepatobiliary malignancy. Evaluation should include laboratory studies and biliary tract imaging. Noninvasive biliary tract imaging can help exclude malignancy and confirm ductal dilation but is not sensitive for Mirizzi syndrome. Endoscopic retrograde cholangiopancreatography can serve both diagnostic as well as therapeutic purposes via stone extraction and stent placement. SpyGlass cholangioscopy can also augment management in the form of Electrohydraulic lithotripsy. Although therapeutic biliary endoscopy can be very effective, cholecystectomy remains the definitive treatment for Mirizzi syndrome.

Cost-Effectiveness Analysis of Primary Arthrodesis Versus Open Reduction Internal Fixation for Primarily Ligamentous Lisfranc Injuries.

The purpose of the present study was to determine whether surgical intervention with open reduction internal fixation (ORIF) or primary arthrodesis (PA) for Lisfranc injuries is more cost effective. We conducted a formal cost-effectiveness analysis using a Markov model and decision tree to explore the healthcare costs and health outcomes associated with a scenario of ORIF versus PA for 45 years postoperatively. The outcomes assessed included long-term costs, quality-adjusted life-years (QALYs), and incremental cost per QALY gained. The costs were evaluated from the healthcare system perspective and are expressed in U.S. dollars at a 2017 price base. ORIF was always associated with greater costs compared with PA and was less effective in the long term. When calculating the cost required to gain 1 additional QALY, the PA group cost $1429/QALY and the ORIF group cost $3958/QALY. The group undergoing PA overall spent, on average, $43,192 less than the ORIF group, and PA was overall a more effective technique. Strong dominance compared with ORIF was demonstrated in multiple scenarios, and the model's conclusions were unchanged in the sensitivity analysis even after varying the key assumptions. ORIF failed to show functional or financial benefits. In conclusion, from a healthcare system's standpoint, PA would clearly be the preferred treatment strategy for predominantly ligamentous Lisfranc injuries and dislocations.

Identification of E-cadherin signature motifs functioning as cleavage sites for Helicobacter pylori HtrA.

The cell adhesion protein and tumour suppressor E-cadherin exhibits important functions in the prevention of gastric cancer. As a class-I carcinogen, Helicobacter pylori (H. pylori) has developed a unique strategy to interfere with E-cadherin functions. In previous studies, we have demonstrated that H. pylori secretes the protease high temperature requirement A (HtrA) which cleaves off the E-cadherin ectodomain (NTF) on epithelial cells. This opens cell-to-cell junctions, allowing bacterial transmigration across the polarised epithelium. Here, we investigated the molecular mechanism of the HtrA-E-cadherin interaction and identified E-cadherin cleavage sites for HtrA. Mass-spectrometry-based proteomics and Edman degradation revealed three signature motifs containing the [VITA]-[VITA]-x-x-D-[DN] sequence pattern, which were preferentially cleaved by HtrA. Based on these sites, we developed a substrate-derived peptide inhibitor that selectively bound and inhibited HtrA, thereby blocking transmigration of H. pylori. The discovery of HtrA-targeted signature sites might further explain why we detected a stable 90 kDa NTF fragment during H. pylori infection, but also additional E-cadherin fragments ranging from 105 kDa to 48 kDa in in vitro cleavage experiments. In conclusion, HtrA targets E-cadherin signature sites that are accessible in in vitro reactions, but might be partially masked on epithelial cells through functional homophilic E-cadherin interactions.

Combinatorial chemistry by ant colony optimization.

BACKGROUND: Prioritizing building blocks for combinatorial medicinal chemistry represents an optimization task. We present the application of an artificial ant colony algorithm to combinatorial molecular design (Molecular Ant Algorithm [MAntA]). RESULTS: In a retrospective evaluation, the ant algorithm performed favorably compared with other stochastic optimization methods. Application of MAntA to peptide design resulted in new octapeptides exhibiting substantial binding to mouse MHC-I (H-2K(b)). In a second study, MAntA generated a new functional factor Xa inhibitor by Ugi-type three-component reaction. CONCLUSION: This proof-of-concept study validates artificial ant systems as innovative computational tools for efficient building block prioritization in combinatorial chemistry. Focused activity-enriched compound collections are obtained without the need for exhaustive product enumeration.