Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

Geología de tos diapiros triásicos en el noreste de la provincia de Murcia.

Main stratigraphic characteristics of triassic diapires: Jumilla, La Celia, Yecla and La Rosa, their tectonics and their environements are studied; all of them are situated in the Northeast Prebetic of Murcia province. Stratigraphically, three stretches are estimated: a detrital-argillaceous-dolomitic one with ocher-yellowish colours in its base, another gypseous-argillaceous intermediate one with vivid red colours and a third one, in the top, with well stratiphied grey scarfed gypsum and some interpolations of dolomites and black clays. Salt ls under the basal stretch and it's developed in most of the up to here studied diapires. As a whole, it's an evaporitic basin in a central position where saline and penesaline litotopes, with tendency to euxinic ones, have been identified. Moreover, we emphasize the existence of volcanic rocks of a lamproitic type which are inserted in the just described materials. From a structural point of view, all these diapires are injected with faults of a regional character; inside them a radial and occasionally concentric fracturation is observed. The "mis en place" of these autcroppings is connected with the main alpine folding stage, Nevertheless, the alocinetic effects work almost to this day providing a neotectonic connected to diapirism which has been displayed on folds , faults and peripheric grooves of materials belonging to Pliocene and Quaternary; in these last ones, old lakes formed where turbidites associated to evaporites settled.Se estudian las principales características estratigráficas de los diapiros triásicos de Jumilla, La Celia, Yecla y La Rosa, así como las tectónicas de los mismos y la de sus alrededores; todos ellos situados en el Prebético del noreste de la provincia de Murcia. Estratigráficamente so aprecian tres tramos: uno detrítico-arcilloso-dolomítico, de colores ocre-amarillentos en la base, otro intermedio yesífero-arcilloso de colores rojos vivos y un tercero, en el techo, de yesos grises bandeados bien estratificados con intercalaciones de dolomías y arcillas negras ; bajo el tramo basal se encuentra la sal común que es explotada en casi todos los diapiros aquí estudiados. En conjunto se trata de una cuenca evaporítica de posición central, en donde han sido identificados los litotopos salino y penesalino con tendencia a euxínico. Es de destacar, además, la presencia de rocas volcánicas del tipo lamproítico encajadas en los materiales descritos. Bajo el punto de vista estructural, todos estos diapiros se han inyectado a favor de fallas de carácter regional y en el interior de los mismos se observa una fracturación radial y ocasionalmente concéntrica. La "mis en place" de estos afloramientos está ligada a la etapa principal del plegamiento alpino; sin embargo , los efectos halocinéticos se dejan sentir hasta épocas recientes, dando lugar a una neotectónica ligada al diapirismo, que se manifiesta en pliegues, fallas y surcos periféricos de materiales pertenecientes al Plioceno y Cuaternario; en estos últimos se instalaron lagos. antiguos en donde pudieron depositarse turbio ditas asociadas a evaporitas

A large testudinid with African affinities in the post-Messinian (lower Pliocene) record of south-eastern Spain

Herein, we describe Alatochelon myrteum gen. et sp. nov., a large tortoise from the post-Messinian (lower Pliocene) of the area of Puerto de la Cadena (Region of Murcia), Spain. The new taxon cannot be attributed to Titanochelon, which represented the only lineage of large tortoises previously recognized in the Neogene record of Europe. Alatochelon myrteum shows African affinities, especially with the extant African spurred tortoise Centrochelys sulcata. Although close phylogenetic relationships have previously been recognized among some tortoises of both continents, the dispersal of this lineage had always been proposed as having occurred in only one direction: from Europe to Africa. The dispersal of the lineage including the new Spanish form and Centrochelys sulcata from Africa to Europe is proposed here. This proposal is compatible with those previously recognized for some lineages of mammals also found in Puerto de la Cadena, identified as African lineages that probably reached Europe during the Messinian Salinity Crisis event. An African origin is also proposed for the lineage of Titanochelon. Therefore, the two lineages of large derived testudinids (i.e. Geochelona) recognized in the European record experienced diachronic dispersal events from Africa to Europe: that to which Alatochelon belongs probably during the Messinian and the other much earlier, at the beginning of the Miocene or before.Fil: Pérez García, Adán. Universidad Nacional de Educacion A Distancia. Facultad de Ciencias.; EspañaFil: Vlachos, Evangelos. Museo Paleontológico Egidio Feruglio; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Murelaga, Xabier. Universidad del País Vasco; Españ

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm