Estudio de moléculas de adhesión y migración en cáncer colorrectal

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Autoimmune responses in oncology: Causes and significance

© 2021 by the authors.Specific anti-tumor immune responses have proven to be pivotal in shaping tumorigenesis and tumor progression in solid cancers. These responses can also be of an autoimmune nature, and autoantibodies can sometimes be present even before the onset of clinically overt disease. Autoantibodies can be generated due to mutated gene products, aberrant expression and post-transcriptional modification of proteins, a pro-immunogenic milieu, anti-cancer treatments, cross-reactivity of tumor-specific lymphocytes, epitope spreading, and microbiota-related and genetic factors. Understanding these responses has implications for both basic and clinical immunology. Autoantibodies in solid cancers can be used for early detection of cancer as well as for biomarkers of prognosis and treatment response. High-throughput techniques such as protein microarrays make parallel detection of multiple autoantibodies for increased specificity and sensitivity feasible, affordable, and quick. Cancer immunotherapy has revolutionized cancer treatments and has made a considerable impact on reducing cancer-associated morbidity and mortality. However, immunotherapeutic interventions such as immune checkpoint inhibition can induce immune-related toxicities, which can even be life-threatening. Uncovering the reasons for treatment-induced autoimmunity can lead to fine-tuning of cancer immunotherapy approaches to evade toxic events while inducing an effective anti-tumor immune response.We gratefully acknowledge financial support from the Spanish Health Institute Carlos III (ISCIII) for grants FIS PI14/01538, FIS PI17/01930, and CB16/12/00400. We also acknowledge Fondos FEDER (EU), Junta Castilla-León (COVID-19 grant COV20EDU/00187), and Fundación Solórzano FS/38-2017. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D + I 2017–2020 and funded by ISCIII and FEDER. A. Landeira-Viñuela is supported by the VIII Centenario-USAL PhD Program. P. Juanes-Velasco is supported by the JCYL PhD Program ‘JCYL Nos Impulsa’ and scholarship JCYL-EDU/601/2020

C-reactive protein cut-off for early tocilizumab and dexamethasone prescription in hospitalized patients with COVID-19

Dexamethasone and tocilizumab have been associated with reduction in mortality, however, the beneficial effect is not for all patients and the impact on viral replication is not well defined. We hypostatized that C-reactive protein (CRP) could help in the identification of patients requiring anti-inflammatory therapy. Patients admitted for > 48 h in our hospital for a confirmed or suspected infection by SARS-CoV-2 from February 2020 to February 2021 were retrospectively evaluated. The primary outcome was mortality at 30 days. Demographics and the most relevant variables related with the outcome were included. CRP was stratified by percentiles. Univariate and multivariate analysis were performed. A total of 3218 patients were included with a median (IQR) age of 66 (74-78) years and 58.9% were males. The rate of intensive care unit admission was 24.4% and the 30-day mortality rate was 11.8%. Within the first 5 days from admission, 1018 (31.7%) patients received dexamethasone and 549 tocilizumab (17.1%). The crude analysis showed a mortality reduction in patients receiving dexamethasone when CRP was > 13.75 mg/dL and > 3.5 mg/dL for those receiving tocilizumab. Multivariate analysis identified the interaction of CRP > 13.75 mg/dL with dexamethasone (OR 0.57; CI 95% 0.37-0.89, P = 0014) and CRP > 3.5 mg/dL with tocilizumab (0.65; CI95%:0.44-0.95, P = 0.029) as independent predictors of mortality. Our results suggest that dexamethasone and tocilizumab are associated with a reduction in mortality when prescribed to patients with a certain inflammatory activity assessed by C-reactive protein

Manual de simulación clínica en especialidades médicas

Manual sobre técnicas y modos de simulación clínica en diversas especialidades médicas.La enseñanza y formación en medicina necesita el uso de la simulación. Existen evidencias de su uso desde hace cientos de años, pero, en los últimos años se ha incrementado y diseminado. La simulación clínica está validada científicamente en múltiples contextos médicos y de otras áreas profesionales de la salud. Y es considerada de gran importancia como proceso de entrenamiento y de mejora de las competencias y adquisición de habilidades médicas en campos que incluye desde la historia clínica, comunicación con el paciente, exploración, diagnóstico terapéutica médica-farmacológica y quirúrgica y seguridad al tratar al paciente. Hoy en día, para muchas técnicas y situaciones clínicas es inaceptable llegar junto a los pacientes sin un dominio adquirido en simulación. La simulación puede ocurrir sin el uso de recursos adicionales, solo las personas, o utilizando pocos o muchos recursos de baja hasta alta tecnología y se puede adaptar a los recursos disponibles, abarcando todas las áreas de conocimiento, y dentro de ellas competencias técnicas o actitudes, solas o en conjunto. El uso racional y basado en evidencia de la simulación es de la mayor importancia por la necesidad de una mayor efectividad y eficiencia en la transformación de los profesionales de la salud para que puedan mejorar su capacidad de atender a los pacientes. La simulación es también una buena herramienta de evaluación de competencias y habilidades en Medicina y otras disciplinas de las Ciencias de la Salud Este manual incluye técnicas y modos de simulación clínica en diversas especialidades médicas, útiles, para quien busque un manual práctico y actualizado.Cátedra de Mecenazgo de la Universidad de Málaga. Cátedra de Terapias Avanzadas en Patología Cardiovascular Cátedra de Mecenazgo de la Universidad de Málaga. Cátedra de Investigación Biomédica Quirón Salu

Response to Treatment with an Anti-Interleukin-6 Receptor Antibody (Tocilizumab) in a Patient with Hemophagocytic Syndrome Secondary to Immune Checkpoint Inhibitors

Background. Immunotherapy represents one of the fundamental treatments in the management of some types of cancer, especially malignant melanoma. Toxicity derived from increased immune system activity can manifest in multiple organs and systems. We present a case of hematological toxicity, manifested as hemophagocytic syndrome (HPS), which was successfully treated with an anti-interleukin-6 antibody (tocilizumab). Case Report. This case presents a 75-year-old woman diagnosed with metastatic choroidal melanoma, refractory to several lines of treatment. After the failure of the previous lines, ipilimumab was started. After the third dose, she developed grade 2 thrombocytopenia and anemia accompanied by elevated levels of ferritin, triglycerides, and decreased fibrinogen. Hemophagocytosis was observed in the bone marrow biopsy, and a PET-CT showed splenomegaly with increased metabolism. Treatment was based on high doses of corticosteroids and tocilizumab. Four days after the start of treatment, progressive clinical and analytical improvement was observed, achieving total remission of the condition. Discussion. HPS induced by immunotherapy is due to an immunorelated cytokine storm syndrome (CSS). The administration of the anti-interleukin-6 receptor antibody drug acted on this cytokine cascade, leading to stabilization and subsequent remission. For this reason, the use of tocilizumab should be part of the immunotherapy-induced HPS treatment algorithm

Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis

Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system’s involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of mutations in the main genes of the MMR system (MLH1, MSH2, MSH6, and PMS2). This work retrospectively assessed the role that these gene mutations play in the response to and survival of ICIs in NSCLC. Patients with NSCLC treated with nivolumab as the second-line treatment in the University Hospital of Salamanca were enrolled in this study. Survival and response analyses were performed according to groups of MMR system gene expression (MMR expression present or deficiency) and other subgroups, such as toxicity. There was a statistically significant relationship between the best response obtained and the expression of the MMR system (p = 0.045). The presence of toxicity grade ≥ 3 was associated with the deficiency expression of MMR (dMMR/MSI-H) group (p = 0.022; odds ratio = 10.167, 95% confidence interval (CI) 1.669–61.919). A trend towards greater survival and response to ICIs was observed in NSCLC and dMMR. Assessing the genes in the MMR system involved in NSCLC is key to obtaining personalized immunotherapy treatments

Immunohistochemical Assessment of the P53 Protein as a Predictor of Non-Small Cell Lung Cancer Response to Immunotherapy.

Determining predictive biomarkers for immune checkpoint inhibitors (ICIs) is a current challenge in oncology. Previous studies on non-small cell lung cancer (NSCLC) have shown how TP53 gene mutations are correlated with different responses to ICIs. Strong and diffuse immuno-expression of p53 by immunohistochemistry (IHC) is interpreted as a likely indicator of a TP53 gene mutation. We aimed to assess the p53 protein expression via IHC in NSCLC as a predictive biomarker of the response to ICIs. This was a retrospective hospital-based study of patients with NSCLC treated with Nivolumab in the University Hospital of Salamanca. All diagnostic biopsies were studied via IHC (measuring p53 protein expression, peroxidase anti-peroxidase immunohistochemistry technique using Leica BOND Polymer development kits). Survival analysis was performed by subgroups of expression of p53 and other factors using the Kaplan-Meier estimator and Cox proportional-hazards model. Seventy-three patients were included (59 men and 14 women). The median age was 68 (44-84) years. Thirty-six biopsies were adenocarcinoma, 34 were squamous, and three were undifferentiated. In 41 biopsies (56.2%), the cellular expression of p53 was A trend toward a greater response to ICIs was observed in the PFS and OS of patients with high expression of p53 by IHC (TP53 mutation), especially in the PD-L1 negative adenocarcinoma subgroup. These results will make it possible to make future modifications to the clinical guidelines of NSCLC according to the expression of p53

RecruitNet: A global database of plant recruitment networks

Plant recruitment interactions (i.e., what recruits under what) shape the composition, diversity, and structure of plant communities. Despite the huge body of knowledge on the mechanisms underlying recruitment interactions among species, we still know little about the structure of the recruitment networks emerging in ecological communities. Modeling and analyzing the community-level structure of plant recruitment interactions as a complex network can provide relevant information on ecological and evolutionary processes acting both at the species and ecosystem levels. We report a data set containing 143 plant recruitment networks in 23 countries across five continents, including temperate and tropical ecosystems. Each network identifies the species under which another species recruits. All networks report the number of recruits (i.e., individuals) per species. The data set includes >850,000 recruiting individuals involved in 118,411 paired interactions among 3318 vascular plant species across the globe. The cover of canopy species and open ground is also provided. Three sampling protocols were used: (1) The Recruitment Network (RN) protocol (106 networks) focuses on interactions among established plants ("canopy species") and plants in their early stages of recruitment ("recruit species"). A series of plots was delimited within a locality, and all the individuals recruiting and their canopy species were identified; (2) The paired Canopy-Open (pCO) protocol (26 networks) consists in locating a potential canopy plant and identifying recruiting individuals under the canopy and in a nearby open space of the same area; (3) The Georeferenced plot (GP) protocol (11 networks) consists in using information from georeferenced individual plants in large plots to infer canopy-recruit interactions. Some networks incorporate data for both herbs and woody species, whereas others focus exclusively on woody species. The location of each study site, geographical coordinates, country, locality, responsible author, sampling dates, sampling method, and life habits of both canopy and recruit species are provided. This database will allow researchers to test ecological, biogeographical, and evolutionary hypotheses related to plant recruitment interactions. There are no copyright restrictions on the data set; please cite this data paper when using these data in publications

RecruitNet: A global database of plant recruitment networks

Plant recruitment interactions (i.e., what recruits under what) shape the composition, diversity, and structure of plant communities. Despite the huge body of knowledge on the mechanisms underlying recruitment interactions among species, we still know little about the structure of the recruitment networks emerging in ecological communities. Modeling and analyzing the community-level structure of plant recruitment interactions as a complex network can provide relevant information on ecological and evolutionary processes acting both at the species and ecosystem levels. We report a data set containing 143 plant recruitment networks in 23 countries across five continents, including temperate and tropical ecosystems. Each network identifies the species under which another species recruits. All networks report the number of recruits (i.e., individuals) per species. The data set includes >850,000 recruiting individuals involved in 118,411 paired interactions among 3318 vascular plant species across the globe. The cover of canopy species and open ground is also provided. Three sampling protocols were used: (1) The Recruitment Network (RN) protocol (106 networks) focuses on interactions among established plants (“canopy species”) and plants in their early stages of recruitment (“recruit species”). A series of plots was delimited within a locality, and all the individuals recruiting and their canopy species were identified; (2) The paired Canopy-Open (pCO) protocol (26 networks) consists in locating a potential canopy plant and identifying recruiting individuals under the canopy and in a nearby open space of the same area; (3) The Georeferenced plot (GP) protocol (11 networks) consists in using information from georeferenced individual plants in large plots to infer canopy-recruit interactions. Some networks incorporate data for both herbs and woody species, whereas others focus exclusively on woody species. The location of each study site, geographical coordinates, country, locality, responsible author, sampling dates, sampling method, and life habits of both canopy and recruit species are provided. This database will allow researchers to test ecological, biogeographical, and evolutionary hypotheses related to plant recruitment interactions. There are no copyright restrictions on the data set; please cite this data paper when using these data in publications