TTCC-2019-02: real-world evidence of first-line cetuximab plus paclitaxel in recurrent or metastatic squamous cell carcinoma of the head and neck

ObjectivesThe aim of this study was to confirm the efficacy of the ERBITAX scheme (paclitaxel 80 mg/m2 weekly and cetuximab 400 mg/m2 loading dose, and then 250 mg/m2 weekly) as first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) who are medically unfit for cisplatin-based (PT) chemotherapy.Materials and methodsThis retrospective, non-interventional study involved 16 centers in Spain. Inclusion criteria were to have started receiving ERBITAX regimen from January 2012 to December 2018; histologically confirmed SCCHN including oral cavity, oropharynx, hypopharynx, and larynx; age ≥18 years; and platinum (PT) chemotherapy ineligibility due to performance status, comorbidities, high accumulated dose of PT, or PT refractoriness.ResultsA total of 531 patients from 16 hospitals in Spain were enrolled. The median age was 66 years, 82.7% were male, and 83.5% were current/former smokers. Patients were ineligible to receive PT due to ECOG 2 (50.3%), comorbidities (32%), PT cumulative dose ≥ 225 mg/m2 (10.5%), or PT refractoriness (7.2%). Response rate was 37.7%. Median duration of response was 5.6 months (95% CI: 4.4–6.6). With a median follow-up of 8.7 months (95% CI: 7.7–10.2), median PFS and OS were 4.5 months (95% CI: 3.9–5.0) and 8.9 months (95% CI: 7.8–10.3), respectively. Patients treated with immunotherapy after ERBITAX had better OS with a median of 29.8 months compared to 13.8 months for those who received other treatments. The most common grade ≥ 3 toxicities were acne-like rash in 36 patients (6.8%) and oral mucositis in 8 patients (1.5%). Five (0.9%) patients experienced grade ≥ 3 febrile neutropenia.ConclusionThis study confirms the real-world efficacy and tolerability of ERBITAX as first-line treatment in recurrent/metastatic SCCHN when PT is not feasible. Immunotherapy after treatment with ERBITAX showed remarkable promising survival, despite potential selection bias

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Caracterización molecular e isotópica de espeleotemas de tubos de lava de Lanzarote con interés para la astrobiología y conservación

9 páginas.- 5 figuras.- 15 referencias.- Comunicación oral presentada en el VIII Congreso Español sobre Cuevas y Minas Turísticas "Minas y Cuevas: Patrimonio Geológico y Turístico". J.M. Calaforra y J.J. Durán Valsero (eds.), Pulpí (Almería) 19-22 octubre 2022.- Enlace al libro de Actas completo https://www.cuevasturisticas.es/actas-cuevatur-2022Las cuevas volcánicas han atraído durante los últimos años el interés científico por la detección de cuevas similares en la Luna y Marte. La isla volcánica de Lanzarote (Canarias, España) alberga una extraordinaria variedad de cavidades formadas durante diferentes procesos volcánicos. De hecho, el tubo de lava La Corona es uno de los más grandes conocidos en la Tierra, y presenta innumerables analogías con los tubos de lava de la Luna y Marte. El objetivo principal de este trabajo, realizado en el marco del proyecto TUBOLAN, fue estudiar la composición molecular de la fracción orgánica, concretamente los compuestos lipídicos, aislados en espeleotemas de diferentes tubos de lava de la isla de Lanzarote, con el fin de entender como las firmas biológicas se preservan en el registro geológico y pueden servir de modelos para la búsqueda en un futuro próximo de vida microbiana en tubos de lava del planeta rojo. Para este estudio se han analizado 6 muestras de espeleotemas de 5 cuevas diferentes mediante técnicas de cromatografía de gases, espectrometría de masas, pirolisis analítica y espectrometría de relaciones isotópicas de carbono y nitrógeno (e.g., GC/MS, Py- GC/MS y EA/IRMS). La distribución observada de los alcanos lineales de bajo peso molecular se relacionó con un origen microbiano, hecho que fue confirmado por la presencia de ácidos grasos metilados de cadena corta (C<20). Por otro lado, la existencia de ciertos compuestos lipídicos de alto peso molecular considerados biomarcadores de vegetación superficial, mostró cierta influencia de la vegetación existente en la superficie sobre las cuevas. Estos compuestos pueden haber sido incorporados mediante procesos de lixiviación superficial. Estos resultados fueron confirmados mediante el estudio de los isótopos estables de carbono y nitrógeno. El valor medido de δ13C -24 ‰ en los extractos es característico de vegetación con fotosistema del tipo C3, mientras que valores de δ15N cercanos a 0 ‰ indicarían la presencia de fertilizantes inorgánicos, utilizados en las zonas de cultivo de la vid existentes sobre la cueva. El estudio de la composición lipídica y de isótopos estables de la fracción orgánica de los espeleotemas de cuevas volcánicas de la Isla de Lanzarote puede ser de utilidad para identificar vestigios de vida (presente y pasada), así como las alteraciones sufridas, ya sea por cambios ambientales o antrópicosEsta publicación es parte del proyecto de investigación TUBOLAN PID2019-108672RJ- I00 y del contrato Ramón y Cajal (RYC2019-026885-I), financiados por el Ministerio de Ciencia e Innovación MCIN/AEI/10.13039/501100011033. Además, este trabajo ha recibido apoyo de la Fundação para a Ciencia e Tecnología de Portugal (FCT), en el marco del proyecto MICROCENO (PTDC/CTA-AMB/0608/2020), y del Consejo Superior de Investigaciones Científicas (CSIC) a través del proyecto intramural PIE_20214AT021. Los autores también agradecen al Parque Nacional Timanfaya y al Geoparque de Lanzarote su cooperación imprescindible para poder llevar a cabo la toma de muestras en los tubos de lava. Se agradece al espeleólogo Gustavo Santana, por su inestimable colaboración durante la campaña de exploración en la Cueva de las Breñas.N

Microbial inhabitants and biosignatures of volcanic caves from macaronesia

Trabajo presentado en la 4th International Planetary Caves Conference, celebrada en Lanzarote (España) del 04 al 07 de mayo de 2023.[Introduction]: Caves are exceptional habitats for highly specialized microorganisms that can interact with minerals, allowing us to better understand the role of microorganisms in biogeochemical cycles and biomineralization processes. These priceless subterranean resources can be found all over the world, but they are one of the least explored habitats on Earth. Yet, lava caves have recently received special attention due to the discovery of numerous volcanic cave entrances on the Moon and Mars [1]. Such subsurface geological settings, characterized by stable physicochemical conditions, may support microbial activity over geological timescales, resulting in the preservation of traces of life in the rock record, recognized as biosignatures. These subterranean environments and the microbial life within thus provide a unique opportunity to study extremely specialized microorganisms, novel metabolic strategies, and interactions with igneous rocks relevant to astrobiology and planetary sciences.[Methods]: The diversity and function of microbial communities dwelling on speleothems from volcanic caves of Selvagens Islands (Madeira, Portugal), La Palma and Lanzarote (Canary Islands, Spain) have been investigated using portable cutting-edge DNAbased analysis, complemented by in-depth metagenomics and field emission scanning electron microscopy (FESEM), to understand which microorganisms grow in these extreme ecosystems, which functional properties they have, and their role in constructive and/or destructive mineral processes. In addition, advanced chromatography, and mass spectrometry techniques, such as GC/MS, PyrolysisGC/Q-TOF and Pyrolysis-compound specific isotope analysis (Py-CSIA) have been employed for an indepth biogeochemical characterization of the siliceous speleothems and for the assessment of biosignatures preserved in the samples, as described in Miller et al. [2,3].[Results and Discussion]: Bacterial communities showed heterogeneity in composition among lava tubes, with the Actinomycetota, Bacillota and Bacteroidota phyla as the most abundant, exceeding 50% for most of the sampling sites. Using FESEM, we described the morphology of microbial cells and their interactions with the mineral substrate. FESEM images showed abundant actinobacteria-like cells and other morphotypes, resembling those reported by Riquelme et al. [4] in lava tubes from USA, Canada, Portugal and Spain, and in Etna lava tubes [5]. Observations conducted on microbial mat samples from a lava tube in Lanzarote revealed the presence of Ca-rich spheroids closely associated with filamentous cells of Crossiella sp.. The functional profile of microbial communities predicted by PICRUSt showed the presence of urease enzyme, that has been identified as responsible for the microbial precipitation of CaCO3 via urea hydrolysis [6], suggesting that this genus could promote speleothem formation. Similar biogenic-like CaCO3 microspheres were reported in colored microbial mats from Kipuka Kanohina lava cave in Hawaii, USA [4]. The presence of short-chain n-alkanes (C<20) and methylated fatty acids identified in the organic fraction of the siliceous speleothems are recognized as biosignatures of microbial origin (membrane lipids and/or microbial metabolites). High molecular weight lipid compounds (e.g., sterols and long-chain nalkanes) are indicative of vegetation biomarkers derived from lixiviation processes of the soil overlying cavesThis study has been funded by the Spanish Ministry of Science and Innovation from the Spanish State Agency through the TUBOLAN (PID2019 108672RJ-I00) and HIRES-SOM (TED2021-130683B-C22) projects. The Portuguese Foundation for Science and Technology (FCT) and the Regional Government of Andalusia (Spain) are also acknowledged for funding the MICROCENO (PTDC/CTA-AMB/0608/2020) and MICROLAVA (PROYEXCEL_00185) projects, respectively. The Spanish National Research Council (CSIC) is acknowledged for funding the intramural project PIE_20214AT021. A.Z.M and N.T.J-M. thank the Ramón y Cajal research contracts (RYC2019-026885-I and RyC2021-031253-I, respectively).Peer reviewe