PCIG: a web-based application to explore immune–genomics interactions across cancer types

Cancer; Application; Genomic alterationsCáncer; Aplicación; Alteraciones genómicasCàncer; Aplicació; Alteracions genòmiquesMotivation Genomic alterations can modulate the tumor immunophenotype depending on their nature and tissue of origin. Although this immune–genomic interaction may shape disease progression and response to immunotherapy, the factors governing such dynamics and the influence of each tissue-specific context remain poorly understood. Results Here, we have developed the PanCancer ImmunoGenomics (PCIG) tool, a web-based resource that provides researchers with the opportunity to mine immunome–genome relationships across several cancer types using data from the Pan-Cancer Analysis of Whole-Genomes (PCAWG) study, which comprises >2,600 samples spanning across 20 different cancer primary sites. PCIG yields an integrative analysis of the crosstalk between somatic genomic alterations and different immune features, thus helping to understand immune response-related processes.This work was supported by the Instituto de Salud Carlos III and co-funded by the European Regional Development Fund (ERDF) [CPII18/00026, PI17/01304], the CIBEREHD and CIBERNED programs from Instituto de Salud Carlos III, the Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya [2017 SGR 1035], and Fundación Científica de la Asociación Española Contra el Cáncer [GCB13131592CAST]. S.L. obtained a PFIS grant from Instituto de Salud Carlos III and co-funded by the European Regional Development Fund (ERDF) [FI18/00221]. R.E.F. is supported by a doctoral training grant from MICINN/MINECO [BES-2017-081286] and a mobility grant from Fundació Universitària Agustí Pedro i Pons. This article is based upon work from COST Action [CA17118] and supported by COST (European Cooperation in Science and Technology)

Efficacy of chemotherapy for malignant pleural mesothelioma according to histology in a real-world cohort

Cancer therapy; MesotheliomaTerapia del cáncer; MesoteliomaTeràpia del càncer; MesoteliomaCheckMate 743 trial demonstrated survival benefit of immunotherapy in first line in MPM with some differences in the efficacy of chemotherapy according to histology. The objective of this study is to characterize the impact of chemotherapy according to histology in patients diagnosed with MPM at our institution. Clinical records of all MPM patients diagnosed at Vall d’Hebron University Hospital between November 2002 and April 2020 were reviewed. Associations between clinical variables and outcomes were assessed with Cox regression models. Survival data were calculated by the Kaplan–Meier method. 189 patients were included with 76% of tumors classified as epithelioid subtype. First line chemotherapy was offered to 85% of patients. Median survival in overall population was 21.3 months (95% CI 17.2–24.3). We found that patients with epithelioid tumors had better overall survival (OS) and progression free survival (PFS). Median OS of epithelioid patients treated with first line chemotherapy was 26.7 months versus 15.0 months in non-epithelioid patients (HR 2.25 CI 95% 1.4–3.4; p < 0.001). Median PFS for patients with epithelioid tumors treated with chemotherapy was 4.8 months versus 3.6 months in non-epithelioid (HR 1.5 CI 95% 1.0–2.3; p = 0.03). The improvement of outcomes in patients with epithelioid histology was detected in patients treated with cisplatin or carboplatin. Histology was not a predictive factor for the platinum agent sensitivity (p of interaction PFS = 0.09, p of interaction OS = 0.65). In our series, patients with non-epithelioid tumors presented worse prognosis. Although epithelioid tumors exposed to cisplatin had higher PFS, histology was not a clear predictor of chemotherapy efficacy

Phase I prognostic online (PIPO): A web tool to improve patient selection for oncology early phase clinical trials

Immunotherapy; Phase 1 trials; Prognostic modelInmunoterapia; Ensayos de fase 1; Modelo pronósticoImmunoteràpia; Assajos de fase 1; Model pronòsticPurpose Patient selection in phase 1 clinical trials (Ph1t) continues to be a challenge. The aim of this study was to develop a user-friendly prognostic calculator for predicting overall survival (OS) outcomes in patients to be included in Ph1t with immune checkpoint inhibitors (ICIs) or targeted agents (TAs) based on clinical parameters assessed at baseline. Methods Using a training cohort with consecutive patients from the VHIO phase 1 unit, we constructed a prognostic model to predict median OS (mOS) as a primary endpoint and 3-month (3m) OS rate as a secondary endpoint. The model was validated in an internal cohort after temporal data splitting and represented as a web application. Results We recruited 799 patients (training and validation sets, 558 and 241, respectively). Median follow-up was 21.2 months (m), mOS was 10.2 m (95% CI, 9.3–12.7) for ICIs cohort and 7.7 m (95% CI, 6.6–8.6) for TAs cohort. In the multivariable analysis, six prognostic variables were independently associated with OS – ECOG, number of metastatic sites, presence of liver metastases, derived neutrophils/(leukocytes minus neutrophils) ratio [dNLR], albumin and lactate dehydrogenase (LDH) levels. The phase 1 prognostic online (PIPO) calculator showed adequate discrimination and calibration performance for OS, with C-statistics of 0.71 (95% CI 0.64–0.78) in the validation set. The overall accuracy of the model for 3m OS prediction was 87.2% (95% CI 85%–90%). Conclusions PIPO is a user-friendly objective and interactive tool to calculate specific survival probabilities for each patient before enrolment in a Ph1t. The tool is available at https://pipo.vhio.net/.The research leading to these results has received funding from “la Caixa” Foundation (LCF/PR/CE07/50610001). Cellex Foundation for providing research facilities and equipment. This work was supported by the Accelerator Award (UpSMART) from Fundacion Científica – Asociacion Espanola Contra el Cancer (FC -AECC)/ Associazione Italiana per la Ricerca sul Cancro (AIRC) /Cancer Research United Kingdom (CRUK)

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

Disseny d'una aplicació web per a la integració, visualització i anàlisi de les dades genòmiques obtingudes del projecte Pan-Cancer Whole Genome Sequencing (PCAWGS)

Aquest treball de final de màster, situat en l'àmbit de la genòmica del càncer esta basat en les dades del projecte internacional, Pan-Cancer Analyses of Whole Genome Sequences (PCAWGS). Dades fetes publiques recentment que inclouen informació sobre varis anàlisis duts a terme on hi podem trobar més de 2.800 mostres de seqüenciació completa del genoma (Whole Genome Sequencing o WGS), per a diferents tipus de càncer, fins a 40. Entre aquests anàlisis en trobem per exemple: alteracions en nombre de copia (CNA), variants estructurals (SV), dades d'expressió i dades clíniques. En aquest treball s'han utilitzat aquestes dades per a partir d'elles, calcular variables de gran interès en la genòmica del càncer actual, com són l'immunophenoscore (IPS) i les puntuacions de CNA (CNA scores), amb la finalitat d'integrar aquestes noves dades al conjunt de PCAWGS i poder estudiar el paper de les CNAs i SVs en la determinació de les característiques immunitàries del tumor. Com a resultat, s'ha creat una base de dades que relaciona tota aquesta informació i a partir de la qual s'ha desenvolupat una aplicació web amb el framework de Python Django, per tal de proporcionar a grups de recerca clínics una eina de visualització senzilla i intuïtiva, d'on extreure informació sobre les relacions d'aquestes variables en molts tipus de càncer diferents, per poder interpretar i complementar els seus estudis.This master's final project, located in the field of cancer genomics is based on the data of the recently published international project Pan-Cancer Analyzes of Whole Genome Sequences (PCAWGS). This project contains more than 2800 samples of the complete sequencing of the genome (WGS), for up to 40 different types of cancer. This data includes: copy number alterations (CNA), structural variants (SV), expression data and clinical data. In this project we have used PCAWGS data for the calculation of some variables of great interest in the genetics of the current cancer, which are immunophenoscore (IPS) and scores of CNA (BSC and FCS), with the purpose of integrating these new data to the set of PCAWGS and study the impact of CNAs and SVs in the immune characteristics of tumours. As a result, a database was created to contain such calculations and from which a web application has been developed with the Python Django framework, in order to provide clinical research groups a tool of simple and intuitive visualization, to extract information about the relationships of these variables in many different cancer types to interpret and complement their studies.Este trabajo de final de máster, situado en el ámbito de la genómica del cáncer esta basado en los datos del proyecto internacional, Pan-Cancer Analyses of Whole Genome Sequences (PCAWGS). Datos hechos publicas recientemente que incluyen información sobro varios análisis llevados a cabo donde podemos encontrar más de 2.800 muestras de secuenciación completa del genoma (Whole Genome Sequencing o WGS), para diferentes tipos de cáncer, hasta 40. Entre estos análisis encontramos por ejemplo: alteraciones en número de copia (CNA), variantes estructurales (SV), datos de expresión y datos clínicos. En este trabajo se han utilizado estos datos para partir de ellas, calcular variables de gran interés en la genómica del cáncer actual, como son lo immunophenoscore (IPS) y las puntuaciones de CNA (CNA scores), con el fin de integrar estos nuevos datos al conjunto de PCAWGS y poder estudiar el papel de las CNAs y SVs en la determinación de las características inmunitarias del tumor. Como resultado, se ha creado una base de datos que relaciona toda esta información y a partir de la cual se ha desarrollado una aplicación web con lo framework de Python Django, para proporcionar a grupos de investigación clínicos una herramienta de visualización sencilla e intuitiva, de donde extraer información sobre las relaciones de estas variables en muchos tipos de cáncer diferentes, para poder interpretar y complementar sus estudios

El bienestar del docente : vivir bien educando : estrategias para conseguir satisfacción profesional y personal

Resumen basado en el de la publicaciónSe presentan una serie de reflexiones y orientaciones para la elaboración de recursos que permitan al docente vivir de manera positiva su profesión. Estos recursos pretenden 'entrenar' las posibilidades y las formas de aprender y mejorar la salud laboral, destacando la importancia de la inteligencia emocional. Entre las habilidades a potenciar se incluyen: la percepción, el conocimiento y conciencia de las capacidades propias, la confianza y la autoestima, la visión de los conflictos como fuente de mejora de la comunicación y la convivencia y las habilidades sociales.CataluñaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 planta; 28014 Madrid; Tel. +34917748000; [email protected]

Intraoperative transfusion practices in Europe

Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl and increased to 9.8 (1.8) g dl after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold

Intraoperative transfusion practices and perioperative outcome in the European elderly: A secondary analysis of the observational ETPOS study

The demographic development suggests a dramatic growth in the number of elderly patients undergoing surgery in Europe. Most red blood cell transfusions (RBCT) are administered to older people, but little is known about perioperative transfusion practices in this population. In this secondary analysis of the prospective observational multicentre European Transfusion Practice and Outcome Study (ETPOS), we specifically evaluated intraoperative transfusion practices and the related outcomes of 3149 patients aged 65 years and older. Enrolled patients underwent elective surgery in 123 European hospitals, received at least one RBCT intraoperatively and were followed up for 30 days maximum. The mean haemoglobin value at the beginning of surgery was 108 (21) g/l, 84 (15) g/l before transfusion and 101 (16) g/l at the end of surgery. A median of 2 [1–2] units of RBCT were administered. Mostly, more than one transfusion trigger was present, with physiological triggers being preeminent. We revealed a descriptive association between each intraoperatively administered RBCT and mortality and discharge respectively, within the first 10 postoperative days but not thereafter. In our unadjusted model the hazard ratio (HR) for mortality was 1.11 (95% CI: 1.08–1.15) and the HR for discharge was 0.78 (95% CI: 0.74–0.83). After adjustment for several variables, such as age, preoperative haemoglobin and blood loss, the HR for mortality was 1.10 (95% CI: 1.05–1.15) and HR for discharge was 0.82 (95% CI: 0.78–0.87). Preoperative anaemia in European elderly surgical patients is undertreated. Various triggers seem to support the decision for RBCT. A closer monitoring of elderly patients receiving intraoperative RBCT for the first 10 postoperative days might be justifiable. Further research on the causal relationship between RBCT and outcomes and on optimal transfusion strategies in the elderly population is warranted. A thorough analysis of different time periods within the first 30 postoperative days is recommended

Intraoperative transfusion practices in Europe

© 2016 The Author. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.Background: Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. Methods: We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. Results: The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl-1 and increased to 9.8 (1.8) g dl-1 after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Conclusions: Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl-1), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold