Case report: Efficacy of immunotherapy as conversion therapy in dMMR/MSI-H colorectal cancer: a case series and review of the literature

Immunotherapy has demonstrated a role in the therapeutic landscape of a small subset of patients with colorectal carcinoma (CRC) that harbor a microsatellite instability (MSI-H) status due to a deficient DNA mismatch repair (dMMR) system. The remarkable responses to immune checkpoint inhibitors (ICIs) are now being tested in the neoadjuvant setting in localized CRC, where the dMMR/MSI-H status can be found in up to 15% of patients, with remarkable results obtained in NICHE2 and 3 trials, among others. This case series aims to report our experience at a tertiary center and provide a comprehensive analysis of the possible questions and challenges to overcome if ICIs were established as standard of care in a neoadjuvant setting, as well as the potential role they may have as conversion therapy not only in locoregional advanced CRC but also in oligometastatic disease

Scaling properties of binary and greyscale images in the context of X-ray soil tomography

Characterization of the complex soil structure is one the cornerstones of soil science and pore space detection is a crucial step in this process. Synthetic soil image construction has been proved to be an efficient resource for validating different binarization methods given that, unlike in real world, ground truth information is known. In this work, we introduce an improved Truncated Multifractal Method (TMM), to better simulate synthetic computed tomography (CT) soil images and then we generate 150 synthetic images with three different porosities (7%, 12% and 17%), both in greyscale and in binary scale (pore spaces). Synthetic images are then compared with two sets of 260 slides of real CT soil images, in order to validate the goodness of the method. All images are subjected to multifractal analysis where we show a detailed comparative analysis of parameters such as lacunarity, characteristic length and multifractal spectrum, that are calculated both for the whole set of synthetic (greyscale and binary) and for the sets of real CT soil images. With respect to lacunarity, a not previously reported inverse relationship between binary and grey lacunarity is found for this range of porosities. Moreover, we have also reported a new relationship between lacunarity and characteristic length. Similar multifractal results, that we obtain for real CT and synthetic soil images, prove that TMM is a reasonable solution to create simulated CT soil images. Finally, a segmentation test was carried out, using TMM synthetic greyscale soil images and its binary counterpart as ground-truth information, evaluating global (Otsu) and local (Combining Singularity-CA) binarization methods, where we report better performance for the last.Programa Propio (Universidad Politecnica de Madrid)Ministerio de Economia, Industria y Competitividad, Gobierno de España (FIS2017-84151-P)Comunidad de Madrid6.114 JCR (2020) Q1, 3/37 Soil Science1.846 SJR (2020) Q1, 6/140 Soil ScienceNo data IDR 2020UE

Medios de transporte y vías de comunicación : unidad didáctica

Contiene: I.Educación primaria primer ciclo. II.Educación primaria segundo ciclo. III. Educación primaria tercer ciclo. Ejemplares fotocopiados. Fecha de edición aproximada. En la Port. Proyecto de Formación en Centros. Escuelas Rurales y Educación Compensatoria.Unidad didáctica sobre los medios de transporte y comunicación desarrollada en el área de conocimiento del medio en los tres ciclos de la educación primaria. En cada ciclo se exponen los objetivos, los contenidos conceptuales, procedimentales y actitudinales, junto con las actividades adaptadas a cada ciclo..Castilla La ManchaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Her-2 Targeted Therapy in Advanced Urothelial Cancer: From Monoclonal Antibodies to Antibody-Drug Conjugates

Metastatic urothelial cancer, associated with a poor prognosis, is still major cause of cancer-related death, with scarce options of effective treatment after progression to platinum-based chemotherapy and immunotherapy. The human epithelial growth factor receptor 2 (Her-2) has been identified as a new therapeutic target in medical oncology. However, despite the encouraging results in breast and gastric cancers, clinical trials with anti-Her-2 monoclonal antibodies and tyrosine-kinase inhibitors have shown limited efficacy of this strategy in urothelial tumors. Notably, more favorable data have been recently shown that antibody-drug conjugates are currently emerging as a novel promising approach for Her-2 targeted therapy in advanced urothelial cancer

Localized Colonic Small-Cell Carcinoma with Pathological Complete Response after Neoadjuvant Cisplatin and Etoposide: A Case Report

Extrapulmonary small-cell carcinoma (SCC) is a rare neoplasm that shares certain features with its pulmonary counterpart and occurs predominantly in the gastrointestinal tract (GIT). It is a high-grade and poorly differentiated neuroendocrine tumor, usually diagnosed in advanced stages, with a poor prognosis and few therapeutic options in that setting. This is a case report of a 77-year-old Spanish male patient with localized SCC of the colon, who presented a pathological complete response in the surgical specimen after neoadjuvant chemotherapy with cisplatin and etoposide. To date, 5 years after surgery, the patient remains without evidence of tumor recurrence. As clinical guidelines for the management of this entity are lacking, and therefore its management has not been standardized, an attempt to summarize the current evidence in the literature was made

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols