The volume of ERCP per endoscopist is associated with a higher technical success and a lower post-ERCP pancreatitis rate. A prospective analysis

Introduction: conflicting results have been reported regarding the influence of the annual volume of endoscopic retrograde cholangiopancreatography (ERCP) on outcome. Objective: to evaluate the influence of case volume on ERCP outcomes. Patients and methods: an analysis of a prospective database was performed, comparing the outcomes of ERCP in three consecutive periods defined by the number of endoscopists performing ERCP: five endoscopists in period I (P1), four in period II (P2) and three in period III (P3). Only patients with biliary ERCP in accessible and naïve papilla were included. Primary variables were cannulation rates and adverse effects (AE). The American Society of Gastrointestinal Endoscopy (ASGE) complexity grades III and IV were considered as highly complex procedures. Results: a total of 2,561 patients were included: 727 (P1), 972 (P2) and 862 (P3). There were no differences in age and sex between groups (p > 0.05). The cannulation rate was significantly higher in P2 and P3: 92.4 % vs 93.3 % vs 93 % (p = 0.037). The AE rate was 13.8 %, 12.6 % and 10.3 % (p > 0.05), respectively. The rate of post-ERCP pancreatitis was significantly lower in P3: 8.5 %, 7.3 % and 5 % (p = 0.01). The rate of complex procedures was 12 %, 14.8 % and 27 % (p < 0.0001), respectively. Two endoscopists participated in all periods and only one had significantly improved outcomes. Cannulation and post-ERCP pancreatitis rates remained significantly better in P3 after adjusting for sex, complexity and endoscopist. Conclusion: a higher annual volume of ERCP per endoscopist was associated with a higher rate of cannulation and a lower rate of post-ERCP pancreatitis, despite the greater complexity of the procedures. These beneficial effects seem to differ between endoscopists

A dentary fragment of an iguanodontoid ornithopod (Dinosauria) from the Early Cretaceous of Salas de los Infantes (Burgos, Spain) in the collections of the Institut für Geowissenschaften of Tübingen (Germany)

A dentary fragment that preserves several teeth in situ of an ornithopod dinosaur from the Lower Cretaceous of Salas de los Infantes (Burgos, Spain) is described. The general aspect and the conservation of the rock associated with the fossil suggest that it would come from the Pinilla de los Moros Formation (upper Hauterivian-lower Barremian). The material takes part, together with other fossils of dinosaurs and crocodilians, of a collection gathered at the end of the 1960’s and deposited nowadays in the Institut für Geowissenschaften of the University of Tübingen (Germany). The dentary teeth exhibit a distal primary ridge and a mesial secondary ridge, as typically in basal iguanodontoids. Nevertheless, some teeth show a single subcentral carina and lack subsidiary ridges, as in hadrosaurids. Unlike hadrosaurids, however, the Salas specimen has probably one functional tooth and one replacement crown per dentary tooth position, retaining the plesiomorphic state present in basal iguanodontoids. Due to the fragmentary nature of the material, it is provisionally assigned to Iguanodontoidea inde

Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures

Objective: despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA). Design: a prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay. Results: an initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut. Conclusion: implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies.Funding: we thank the financial support of CIBERehd; grants PI16/01126 and PI19/00163 from Instituto de Salud Carlos III (ISCIII) cofinanced by ’Fondo Europeo de Desarrollo Regional’ (FEDER) ’Una manera de hacer Europa’; grants 58/2017 and 55/2018 from Gobierno de Navarra Salud; grant 0011-1411-2020-000010 from AGATA Strategic Project from Gobierno de Navarra; grant 2020/101 from Euroregion Nouvelle Aquitaine-Euskadi-Navarra; Fundación Eugenio Rodríguez Pascual; Fundación Mario Losantos, Fundación M Torres; grant 2018/117 from AMMF, the Cholangiocarcinoma Charity; the COST Action CA181122 Euro-cholangio-Net; POSTD18014AREC postdoctoral fellowship from AECC to MA; and Ramón y Cajal Program contracts RYC-2014-15242 and RYC-2018-024475-1 to FJC and MGFB

Pilot multi-omic analysis of human bile from benign and malignant biliary strictures: a machine-learning approach

Cholangiocarcinoma (CCA) and pancreatic adenocarcinoma (PDAC) may lead to the development of extrahepatic obstructive cholestasis. However, biliary stenoses can also be caused by benign conditions, and the identification of their etiology still remains a clinical challenge. We performed metabolomic and proteomic analyses of bile from patients with benign (n = 36) and malignant conditions, CCA (n = 36) or PDAC (n = 57), undergoing endoscopic retrograde cholangiopancreatography with the aim of characterizing bile composition in biliopancreatic disease and identifying biomarkers for the differential diagnosis of biliary strictures. Comprehensive analyses of lipids, bile acids and small molecules were carried out using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (1H-NMR) in all patients. MS analysis of bile proteome was performed in five patients per group. We implemented artificial intelligence tools for the selection of biomarkers and algorithms with predictive capacity. Our machine-learning pipeline included the generation of synthetic data with properties of real data, the selection of potential biomarkers (metabolites or proteins) and their analysis with neural networks (NN). Selected biomarkers were then validated with real data. We identified panels of lipids (n = 10) and proteins (n = 5) that when analyzed with NN algorithms discriminated between patients with and without cancer with an unprecedented accuracy.This research was funded by: Instituto de Salud Carlos III (ISCIII) co-financed by Fondo Europeo de Desarrollo Regional (FEDER) Una manera de hacer Europa, grant numbers: PI16/01126 (M.A.A.), PI19/00819 (M.J.M. and J.J.G.M.), PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 (J.M.B.); Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation), grant name: Rare Cancers 2017 (J.M.U., M.L.M., J.M.B., M.J.M., R.I.R.M., M.G.F.-B., C.B., M.A.A.); Gobierno de Navarra Salud, grant number 58/17 (J.M.U., M.A.A.); La Caixa Foundation, grant name: HEPACARE (C.B., M.A.A.); AMMF The Cholangiocarcinoma Charity, UK, grant number: 2018/117 (F.J.C. and M.A.A.); PSC Partners US, PSC Supports UK, grant number 06119JB (J.M.B.); Horizon 2020 (H2020) ESCALON project, grant number H2020-SC1-BHC-2018–2020 (J.M.B.); BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia, grant numbers BIO15/CA/016/BD (J.M.B.) and BIO15/CA/011 (M.A.A.). Department of Health of the Basque Country, grant number 2017111010 (J.M.B.). La Caixa Foundation, grant number: LCF/PR/HP17/52190004 (M.L.M.), Mineco-Feder, grant number SAF2017-87301-R (M.L.M.), Fundación BBVA grant name: Ayudas a Equipos de Investigación Científica Umbrella 2018 (M.L.M.). MCIU, grant number: Severo Ochoa Excellence Accreditation SEV-2016-0644 (M.L.M.). Part of the equipment used in this work was co-funded by the Generalitat Valenciana and European Regional Development Fund (FEDER) funds (PO FEDER of Comunitat Valenciana 2014–2020). Gobierno de Navarra fellowship to L.C. (Leticia Colyn); AECC post-doctoral fellowship to M.A.; Ramón y Cajal Program contracts RYC-2014-15242 and RYC2018-024475-1 to F.J.C. and M.G.F.-B., respectively. The generous support from: Fundación Eugenio Rodríguez Pascual, Fundación Echébano, Fundación Mario Losantos, Fundación M Torres and Mr. Eduardo Avila are acknowledged. The CNB-CSIC Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0001 (F.J.C.). Comunidad de Madrid Grant B2017/BMD-3817 (F.J.C.).Peer reviewe

Unusual sauropod tracks in the Jurassic-Cretaceous interval: Cameros Basin (Burgos, Spain)

The Las Sereas site includes at least 14 ichnological outcrops along 5.6 km, in the Lara area, southwest Burgos Province. 67 ichnites of dinosaurs are documented at Las Sereas 7, identified as theropod and sauropod trackways occurring in shallow carbonates of lacustrine environment. Sauropod trackways have intermediate-gauge and low heteropody, and show different anatomical features to other tracks found in the ichnological record, especially in the disposition and orientation of pes digits. They are similar to Polyonyx from the Middle Jurassic of Portugal. However, since they do not preserve reliable manus data they are classified as aff. Polyonyx. The three sauropod trackways are related to the same kind of trackmaker. They differ from each other only in size, and gregarious behavior has not been detected. Analysis of these trackways reveals changes in travel direction even when there are few tracks in each sequence. At the Las Sereas 7 tracksite, the pace length (PL), width of the angulation pattern (WAP) and the WAP/PL ratio and depth analysis via photogrammetry show a direction change in two sauropod trackways. This tracksite and that at La Pedraja are unique in the Tithonian-Berriasian interval of the Iberian Peninsula that occur in a lacustrine environment, and could be indicate of the relationship between the diversity of Iberian, Tithonian-Berriasian sauropod tracks and sedimentary environments.El yacimiento de Las Sereas se compone de al menos 14 afloramientos icníticos que se localizan a lo largo de 5,6 Km de longitud en la comarca de Lara, en el sureste de la provincia de Burgos. En el afloramiento de Las Sereas 7 se han documentado 67 icnitas de dinosaurios, identificadas como terópodas y saurópodas, producidas en un ambiente lacustre carbonatado somero. Las rastros saurópodos son de anchura intermedia y heteropodia baja mostrando caracteres anatómicos diferentes a los encontrados en el registro icnológico conocido, en especial en lo referente a la disposición y orientación de los dedos del pie. La mayor semejanza de estas icnitas saurópodas se establece con Polyonyx del Jurásico Medio de Portugal, pero al carecer de datos fiables sobre la anatomía de las manos en Las Sereas, clasificamos estas icnitas de Burgos como aff. Polyonyx. Los tres rastros saurópodos de Burgos se atribuyen a un mismo icnopoyeta, diferenciándose entre sí sólo por el tamaño, y sin que se haya detectado un comportamiento gregario. En el estudio de estos rastros pueden recogerse datos que informen sobre trayectos con cambio de dirección, incluso cuando lo que se conserva es una serie relativamente corta de pasos. En Las Sereas 7 la combinación de los valores de varios parámetros –longitud de paso (PL), pauta de anchura de angulación (WAP) y relación WAP/PL– y el estudio de la profundidad de las icnitas por fotogrametría permiten interpretar un cambio de dirección en dos de los rastros saurópodos. Este yacimiento y el de La Pedraja son los únicos conocidos en el registro del intervalo Titoniense-Berriasiense de la Península Ibérica que se formaron en un medio lagunar. En este sentido, podría haber una relación entre la diversidad de icnitas saurópodas ibéricas del intervalo Titoniense-Berriasiense y la presencia de éstas en distintos medios sedimentarios.Fil: Torcida Fernández Baldor, F.. Museo de Dinosaurios de Salas de los Infantes y Colectivo Arqueológico Paleontológico de Salas; EspañaFil: Díaz Martínez, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Contreras, R.. Museo de Dinosaurios de Salas de los Infantes y Colectivo Arqueológico Paleontológico de Salas; EspañaFil: Huerta, P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Museo de Dinosaurios de Salas de los Infantes y Colectivo Arqueológico Paleontológico de Salas; España. Universidad Nacional de Río Negro; ArgentinaFil: Montero, D.. Museo de Dinosaurios de Salas de los Infantes y Colectivo Arqueológico Paleontológico de Salas; EspañaFil: Urién, V.. Museo de Dinosaurios de Salas de los Infantes y Colectivo Arqueológico Paleontológico de Salas; Españ