A novel ultrasound-based algorithm for detection of pancreatic stents placed for prophylaxis of post-ERCP pancreatitis: a prospective trial.

PURPOSE: Before removal of retained pancreatic stents placed during endoscopic retrograde cholangiopancreatography to avoid post-ERCP pancreatitis an imaging is recommended. The aim of the present study was to evaluate a new ultrasound-based algorithm. MATERIALS AND METHODS: Patients who received a pancreatic stent for PEP prophylaxis were included. Straight 5Fr (0.035inch) 6cm stents with an external flap that were visualized by ultrasound were removed endoscopically with no further imaging. If the ultrasound result reported the stent to be dislodged or was inconclusive, X-ray imaging was performed. The endpoints were positive and negative predictive value, specificity, sensitivity, and contingency coefficient between ultrasound and X-ray and/or endoscopy. RESULTS: In the present study, 88 patients were enrolled. X-ray was performed in 23 (26%) patients. Accordingly, the ultrasound algorithm saved an X-ray examination in 65 cases, leading to a reduction of 74%. Stents were retained in 67 patients (76%) and visualized correctly by ultrasound in 54 patients with a sensitivity of 81%. The positive predictive value was 83%. Specificity was 48% because ultrasound described 10/21 dislodged stents correctly. The negative predictive value was 43% as 10/23 stents were correctly classified as dislodged by ultrasound. In 11 patients (13%), esophagogastroduodenoscopy was performed even though the pancreatic stent was already dislodged. CONCLUSION: A novel ultrasound-based algorithm reduced the need for X-ray imaging by three quarters. To avoid unnecessary endoscopic examinations, the algorithm should be implemented with a learning phase and procedures should be performed by experienced examiners. An important limitation might be the stent lengths, as shorter stents might be more difficult to visualize by ultrasound. __________________ Hintergrund: Aktuell wird vor der Entfernung von prophylaktisch gelegten Pankreasstents nach einer endoskopischen retrograden Cholangiopankreatikographie eine Bildgebung empfohlen. Ziel der vorliegenden Studie war es, einen neuen ultraschallbasierten Algorithmus zu evaluieren. MATERIAL UND METHODEN: Eingeschlossen wurden Patienten nach prophylatischer Pankreasstentanalage . Gerade 5 Fr-Stents (0.035 inch) mit 6 cm Länge vom externen Flange, die mittels Ultraschall sichtbar waren, wurden endoskopisch ohne weitere Bildgebung entfernt. Wenn das Ultraschallergebnis den Stent als disloziert beschrieb, wurde eine Röntgenaufnahme durchgeführt. Die Endpunkte waren der positive und negative Vorhersagewert, die Spezifität, Sensitivität und der Kontingenzkoeffizient zwischen Ultraschall und Röntgen und/oder Endoskopie. Ergebnisse: 88 Patienten wurden in die Studie eingeschlossen. Bei 23 (26%) Patienten musste eine Röntgenaufnahme durchgeführt werden. Entsprechend hat der Ultraschallalgorithmus in 65 Fällen (74%) eine Röntgenuntersuchung eingespart. Stents waren bei 67 Patienten (76%) verblieben und wurden bei 54 Patienten korrekt mit einer Sensitivität von 81% mittels Ultraschall visualisiert. Der positive Vorhersagewert betrug 83%. Die Spezifität betrug 48%, da der Ultraschall 10/21 dislozierte Stents korrekt beschrieb. Der negative Vorhersagewert betrug 43%, da 10/23 Stents korrekt als disloziert klassifiziert wurden. Bei 11 Patienten (13%) wurde eine Ösophagogastroduodenoskopie durchgeführt, obwohl der Pankreasstent bereits disloziert war. Fazit: Ein ultraschallbasierter Algorithmus reduzierte den Bedarf an Röntgenbildgebung um drei Viertel. Um unnötige endoskopische Untersuchungen zu vermeiden, sollte der Algorithmus mit einer Lernphase implementiert und das Verfahren von erfahrenen Untersuchern durchgeführt werden. Eine wichtige Einschränkung könnte die Länge der Stents sein, da kürzere Stents mit Ultraschall schwieriger zu visualisieren sein könnten.

Distinct dissociation rates of murine and human norovirus P-domain dimers suggest a role of dimer stability in virus-host interactions.

Norovirus capsids are icosahedral particles composed of 90 dimers of the major capsid protein VP1. The C-terminus of the VP1 proteins forms a protruding (P)-domain, mediating receptor attachment, and providing a target for neutralizing antibodies. NMR and native mass spectrometry directly detect P-domain monomers in solution for murine (MNV) but not for human norovirus (HuNoV). We report that the binding of glycochenodeoxycholic acid (GCDCA) stabilizes MNV-1 P-domain dimers (P-dimers) and induces long-range NMR chemical shift perturbations (CSPs) within loops involved in antibody and receptor binding, likely reflecting corresponding conformational changes. Global line shape analysis of monomer and dimer cross-peaks in concentration-dependent methyl TROSY NMR spectra yields a dissociation rate constant koff of about 1 s-1 for MNV-1 P-dimers. For structurally closely related HuNoV GII.4 Saga P-dimers a value of about 10-6 s-1 is obtained from ion-exchange chromatography, suggesting essential differences in the role of GCDCA as a cofactor for MNV and HuNoV infection.

NMR Experiments Shed New Light on Glycan Recognition by Human and Murine Norovirus Capsid Proteins.

Glycan-protein interactions are highly specific yet transient, rendering glycans ideal recognition signals in a variety of biological processes. In human norovirus (HuNoV) infection, histo-blood group antigens (HBGAs) play an essential but poorly understood role. For murine norovirus infection (MNV), sialylated glycolipids or glycoproteins appear to be important. It has also been suggested that HuNoV capsid proteins bind to sialylated ganglioside head groups. Here, we study the binding of HBGAs and sialoglycans to HuNoV and MNV capsid proteins using NMR experiments. Surprisingly, the experiments show that none of the norovirus P-domains bind to sialoglycans. Notably, MNV P-domains do not bind to any of the glycans studied, and MNV-1 infection of cells deficient in surface sialoglycans shows no significant difference compared to cells expressing respective glycans. These findings redefine glycan recognition by noroviruses, challenging present models of infection.