Herramientas de ayuda a la toma de decisiones en cáncer colorrectal: una revisión

Aim: The objective is to collect available patient decision aids (PDA) for colorectal cancer in any of the stages of the disease and to gather published studies about the use of these tools in the last ten years Methods: A systematic review (SR) of tools for Decision-making Aid in colorectal cancer was performed since year 2000. Search includes main databases (MEDLINE, PsycINFO, EMBASE, Cochrane) as well as websites of institutions working with PDAs to search available tools. Results: After the appraisal of the found articles, we finally selected 10 studies with PDA for colorectal cancer in which patients preferences in the decision making process, disseminating strategies of the tools or the way of presenting patient information were assessed. Through the websites of institutions working with PDAs we found six tools about screening in colorectal cancer. Conclusions: There is a growing interest to involve patients with colorectal cancer in the decision making process. To do so, it’s necessary to assess patients’ values and preferences and that’s why PDAs are effective in helping both, professionals and patients. They are useful for professionals for this assessment process, and also for patients, not just to make a decision but also for being satisfied with the final decisionObjetivo: El objetivo de este trabajo es conocer los estudios publicados es los diez últimos años sobre la utilización de herramientas de ayuda a la toma de decisiones en pacientes con cáncer colorrectal, en cualquiera de las fases de la enfermedad. Así como localizar las herramientas de ayuda a la toma de decisiones que están disponibles. Método: Se ha realizado una revisión de la literatura desde el 2000 hasta el 2010 en las bases MEDLINE, PsycINFO, EMBASE y Cochrane. Así como una búsqueda en páginas webs de distintas organizaciones para la localización de herramientas disponibles Resultados: Una vez realizada la selección de los artículos, se contó con 10 artículos que presentan herramientas, evalúan las preferencias de los pacientes a la hora de tomar decisiones, evalúan las estrategias de distribución de dichas herramientas o se evalúa la forma más eficaz de presentar la información en las herramientas. A través de la búsqueda realizada mediante las páginas webs de las organizaciones se encontraron seis herramientas propiamente dichas sobre el cribado de cáncer colorrectal. Conclusiones: cada vez es mayor el interés por implicar al paciente en la toma de decisiones con respecto al cáncer colorrectal. Para ello se hace necesaria la evaluación de las preferencias y valores de los pacientes y por eso el uso de herramientas de ayuda a la toma de decisiones puede ayudar a los profesionales en esa evaluación y a los pacientes, además de a tomar la decisión, a sentirse satisfecho con ella

Influence of organic matter transformations on the bioavailability of heavy metals

6 páginas, 3 tablas.The agricultural use of anaerobically digested sewage sludge (ADSS) as stable, mature compost implies knowing its total content in heavy metals and their bioavailability. This depends not only on the initial characteristics of the composted substrates but also on the organic matter transformations during composting which may influence the chemical form of the metals and their bioavailability. The objective of this work was to examine the relationships between the changes in the organic matter content and humus fractions, and the bioavailability of heavy metals. A detailed sampling at 0, 14, 84, and 140 days of the composting process was performed to measure C contents in humic acids (HAs), fulvic acids, (FAs) and humin, the total content of Zn, Pb, Cu, Ni, and Cd, and also their distribution into mobile and mobilisable (MB), and low bioavailability (LB) forms. Significant changes of C contents in HA, FA, and Humin, and in the FA/HA, HA/Humin and Chumus/TOC ratios were observed during composting. The MB and LB fractions of each metal also varied significantly during composting. The MB fraction increased for Zn, Cu, Ni, and Cd, and the LB fraction increased for Pb. Stepwise linear regressions and quadratic curve estimation conducted on the MB and LB fractions of each metal as dependent on the measured organic variables suggested that Zn bioavailability was mainly associated to percentage of C in FAs. Bioavailability of Cu, Ni and Cd during composting was associated to humin and HAs. Pb concentration increased in the LB form, and its variations followed a quadratic function with the Chumus/TOC ratio. Our results suggest that the composting process renders the metals in more available forms. The main forms of metal binding in the sludge and their availability in the final compost may be better described when metal fractionation obtained in sequential extraction and humus fractionation during composting are considered together.This work was part of the Generalitat Valenciana projects IIARCO2004-A-196, IIARCO2004-A-212, and IIARCO/2004/213, and the national project 135/2004/3 (Ministerio de Medio Ambiente). We thank FACSA Sewage Treatment Plant (Castellón, Spain), and University Jaume I of Castellón (Spain) for providing materials and technical assistance. We thank the two anonymous reviewers for their useful comments on the manuscript.Peer reviewe

Patient decision aids in colorectl cancer: a review

Aim: The objective is to collect available patient decision aids (PDA) for colorectal cancer in any of the stages of the disease and to gather published studies about the use of these tools in the last ten years Methods: A systematic review (SR) of tools for Decision-making Aid in colorectal cancer was performed since year 2000. Search includes main databases (MEDLINE, PsycINFO, EMBASE, Cochrane) as well as websites of institutions working with PDAs to search available tools. Results: After the appraisal of the found articles, we finally selected 10 studies with PDA for colorectal cancer in which patients preferences in the decision making process, disseminating strategies of the tools or the way of presenting patient information were assessed. Through the websites of institutions working with PDAs we found six tools about screening in colorectal cancer. Conclusions: There is a growing interest to involve patients with colorectal cancer in the decision making process. To do so, it’s necessary to assess patients’ values and preferences and that’s why PDAs are effective in helping both, professionals and patients. They are useful for professionals for this assessment process, and also for patients, not just to make a decision but also for being satisfied with the final decisio

Reutilisation of hazardous spent fluorescent lamps glass waste as supplementary cementitious material

Spent fluorescent lamps glass (SFLG) waste, manually and mechanically processed in a lamps waste treatment plant, was used to partially replace up to 50 wt% Portland cement (PC). Both waste types exhibited similar pozzolanic activity. The mortars containing up to 35 wt% SFLG met the specifications for other pozzolanic materials (e.g. fly ash) and, after 90 curing days, their compressive strength values were similar to or higher than those of the 100% PC sample (58.8 MPa). Our results provide an alternative reutilization process for this hazardous waste to reuse SFLG as-received (no washing to reduce mercury) and contributes to less PC use.Funding for open access charge: CRUE-Universitat Jaume

Dietary flavonoids, lignans and colorectal cancer prognosis

Flavonoids and lignans are polyphenol classes with anticarcinogenic activities against colorectal cancer (CRC). However, very limited epidemiological evidence exists on their effects on CRC prognosis. This study aimed to evaluate the association between flavonoid and lignan intakes with the risk of CRC recurrence and overall survival in CRC patients. The study followed incident histologically confirmed CRC cases in Barcelona (Spain). Validated dietary questionnaires and lifestyle information were collected at recruitment. An ad hoc food composition database on flavonoids and lignans was compiled by using data from the US Department of Agriculture and Phenol-Explorer databases. Adjusted hazards ratios (HR) and 95% confidence intervals (CIs) were estimated using multivariable Cox models. After 8.6 years of mean follow-up, 133 of 409 (32.5%) participants died and 77 of 319 (24.1%) had a CRC recurrence. Total flavonoids were associated neither with CRC recurrence (HR comparing extreme tertiles 1.13, 95% CI 0.64-2.02; P-trend 0.67) nor with overall survival (HR(T3vsT1) 1.06, 95% CI 0.69-1.65; P-trend 0.78) in the multivariable models. No associations were also observed with either total lignans or any flavonoid subclass intake. In conclusion, the results of the current study do not support a role of flavonoid and lignan intake in the CRC prognosis

Carcinoma-associated fibroblasts affect sensitivity to oxaliplatin and 5FU in colorectal cancer cells

The importance of tumor microenvironment (TME) as a relevant contributor to cancer progression and its role in the development of de novo resistance to targeted therapies has become increasingly apparent. However, the mechanisms of microenvironment-mediated drug resistance for nonspecific conventional chemotherapeutic agents, such as platinum compounds or antimetabolites, are still unclear. Here we describe a mechanism induced by soluble factors released by carcinoma-associated fibroblasts (CAFs) that induce the translocation of AKT, Survivin and P38 to the nucleus of tumor cells. These changes are guided to ensure DNA repair and the correct entrance and exit from mitosis in the presence of chemotherapy. We used conditioned media (CM) from normal-colonic fibroblasts and paired CAFs to assess dose response curves of oxaliplatin and 5-fluorouracil, separately or combined, compared with standard culture medium. We also evaluated a colony-forming assay and cell death to demonstrate the protective role of CAF-CM. Immunofluorescence confirmed the translocation of AKT, P38 and Survivin to the nucleus induced by CAF-soluble factors. We also have shown that STAT3 or P38 inhibition provides a promising strategy for overcoming microenvironment-mediated resistance. Conversely, pharmacologic AKT inhibition induces an antagonistic effect that relieves a cMET and STAT3-mediated compensatory feedback that might explain the failure of AKT inhibitors in the clinic so far

La Epigrafía griega y latina en la enseñanza de las materias de Filología Clásica: aplicación de nuevas metodologías y nuevas tecnologías

Informe final del Proyecto de Innovación Docente PIMCD 2016/17-5

Clinical value of prognosis gene expression signatures in colorectal cancer: a systematic review

Introduction: the traditional staging system is inadequate to identify those patients with stage II colorectal cancer (CRC) at high risk of recurrence or with stage III CRC at low risk. A number of gene expression signatures to predict CRC prognosis have been proposed, but none is routinely used in the clinic. The aim of this work was to assess the prediction ability and potential clinical usefulness of these signatures in a series of independent datasets. Methods: a literature review identified 31 gene expression signatures that used gene expression data to predict prognosis in CRC tissue. The search was based on the PubMed database and was restricted to papers published from January 2004 to December 2011. Eleven CRC gene expression datasets with outcome information were identified and downloaded from public repositories. Random Forest classifier was used to build predictors from the gene lists. Matthews correlation coefficient was chosen as a measure of classification accuracy and its associated p-value was used to assess association with prognosis. For clinical usefulness evaluation, positive and negative post-tests probabilities were computed in stage II and III samples. Results: five gene signatures showed significant association with prognosis and provided reasonable prediction accuracy in their own training datasets. Nevertheless, all signatures showed low reproducibility in independent data. Stratified analyses by stage or microsatellite instability status showed significant association but limited discrimination ability, especially in stage II tumors. From a clinical perspective, the most predictive signatures showed a minor but significant improvement over the classical staging system. Conclusions: the published signatures show low prediction accuracy but moderate clinical usefulness. Although gene expression data may inform prognosis, better strategies for signature validation are needed to encourage their widespread use in the clinic

Frequency and Characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain. PATIENTS AND METHODS: An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments. RESULTS: In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups. CONCLUSIONS: Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19 : a multicentre, randomised, double-blind, non-inferiority phase IIb trial

A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with , . From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4 + and CD8 + T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. HIPRA SCIENTIFIC, S.L.U