Factores pronósticos de micosis fungoide: análisis de supervivencia y progresión

La Micosis Fungoide (MF) es un linfoma primario cutáneo epidermotrópico constituido por células T de tamaño pequeño o intermedio con núcleo cerebriforme (1) . En la forma clásica (la más frecuente) se caracteriza por comenzar por áreas en la piel maculosas que evolucionan lentamente a placas infiltradas y posteriormente a estadio tumoral. Ocasionalmente evoluciona de forma agresiva a pesar de las diferentes estrategias terapéuticas. El síndrome de Sézary es una variante agresiva de linfoma T cutáneo con presentación leucémica en el cual se identifican en sangre periférica células malignas (células de Sézary); se define por la triada eritrodermia, linfadenopatía generalizada y la presencia de células neoplásicas clonales T con núcleos cerebriformes en sangre periférica (1) La MF es el linfoma más frecuente de los que se originan en la piel. La edad media de aparición se sitúa entre la 5º y la 6º década. La incidencia está entre 0.5 y 1 caso de cada 100.000 habitantes/año. Se ha multiplicado por 4 en un periodo en que el resto de los linfomas aumentó solo un 16% (2, 3). La mayoría de pacientes muestran un curso clínico indolente durante años. Sin embargo, el pronóstico es muy variable dependiendo del estadio. Cuando hay afectación extracutánea o transformación en un linfoma de alto grado, la mediana de supervivencia es menor de un año (4). La supervivencia a 5 años en estadio de mancha/placa es muy buena, alrededor del 80- 90%, sin embargo cuando aparecen tumores o eritrodermia, ronda el 40% y si se encuentran ganglios afectos, se situa en torno al 30% (4). Dada esta variabilidad y siendo la enfermedad potencialmente letal, es esencial determinar factores pronósticos predictores de la evolución posterior y si fuera posible factores predictores de respuesta a los tratamientos actuales. La ausencia de remisión completa al primer tratamiento con o sin progresión posterior de la enfermedad se relaciona inversamente con las curvas de supervivencia para mortalidad por linfoma y mortalidad total en estos pacientes (5)(6). Tradicionalmente los criterios que han tratado de elucidar el pronóstico contenían estrictamente parámetros clínicos basados en el sistema de estadiaje descrito en 1979 por el MJ Cooperative Group of the American Joint Commmitee on Cancer (AJCC) (ANEXO 1 y 2)(8) este sistema reproducía la forma clásica de valorar el pronóstico tumoral mediante la clasificación T (tamaño o extensión tumoral) , N (afectación ganglionar) y M (afectación visceral), y no fue revisado hasta el año 2005 . Posteriormente en el año 2007 la revisión de esta clasificación por los grupos ISCL/EORTC incluyó en los estadios iniciales, más categorías (7). Pero este sistema aún no ha sido validado, y dentro de un mismo estadio la progresión de los pacientes es diferente..

Molecular Alterations in Pancreatic Cancer: Transfer to the Clinic.

Pancreatic ductal adenocarcinoma (PDA) is the most common cancer of the exocrine pancreas and probably the tumor that has benefited the least from clinical progress in the last three decades. A consensus has been reached regarding the histologic classification of the ductal preneoplastic lesions (pancreatic intra-epithelial neoplasia—PanIN) and the molecular alterations associated with them. Mutations in KRAS and inactivation of CDKN2A, SMAD4 and TP53 are among the most prevalent alterations. Next generation sequencing studies are providing a broad picture of the enormous heterogeneity in this tumor type, describing new mutations less prevalent. These studies have also allowed the characterization of different subtypes with prognostic value. However, all this knowledge has not been translated into a clinical progress. Effective preventive and early diagnostic strategies are essential to improve the survival rates. The main challenge is, indeed, to identify new effective drugs. Despite many years of research and its limited success, gemcitabine is still the first line treatment of PDA. New drug combinations and new concepts to improve drug delivery into the tumor, as well as the development of preclinical predictive assays, are being explored and provide optimism and prospects for better therapies.post-print335 K

Radical scavenging and cellular antioxidant activity of the cocoa shell phenolic compounds after simulated digestion

The cocoa industry generates a considerable quantity of cocoa shell, a by-product with high levels of methylxanthines and phenolic compounds. Nevertheless, the digestion process can extensively modify these compounds’ bioaccessibility, bioavailability, and bioactivity as a consequence of their transformation. Hence, this work’s objective was to assess the influence of simulated gastrointestinal digestion on the concentration of phenolic compounds found in the cocoa shell flour (CSF) and the cocoa shell extract (CSE), as well as to investigate their radical scavenging capacity and antioxidant activity in both intestinal epithelial (IEC-6) and hepatic (HepG2) cells. The CSF and the CSE exhibited a high amount of methylxanthines (theobromine and caffeine) and phenolic compounds, mainly gallic acid and (+)-catechin, which persisted through the course of the simulated digestion. Gastrointestinal digestion increased the antioxidant capacity of the CSF and the CSE, which also displayed free radical scavenging capacity during the simulated digestion. Neither the CSF nor the CSE exhibited cytotoxicity in intestinal epithelial (IEC-6) or hepatic (HepG2) cells. Moreover, they effectively counteracted oxidative stress triggered by tert-butyl hydroperoxide (t-BHP) while preventing the decline of glutathione, thiol groups, superoxide dismutase, and catalase activities in both cell lines. Our study suggests that the cocoa shell may serve as a functional food ingredient for promoting health, owing to its rich concentration of antioxidant compounds that could support combating the cellular oxidative stress associated with chronic disease developmentThis research was funded by the COCARDIOLAC project from the Spanish Ministry of Science and Innovation (RTI 2018-097504-B-I00) and the Excellence Line for University Teaching Staff within the Multiannual Agreement between the Community of Madrid and the UAM (2019–2023). M. Rebollo-Hernanz received funding from the FPU program of the Ministry of Universities for his predoctoral fellowship (FPU15/04238) and a grant for the requalification of the Spanish university system (CA1/RSUE/2021-00656

Expert consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the determination of biomarkers in pancreatic and biliary tract cancer

Biliary tract cancer; Predictive value; Targeted therapiesCáncer de vías biliares; Valor predictivo; Terapias dirigidasCàncer de vies biliars; Valor predictiu; Teràpies dirigidesPancreatic cancer and biliary tract cancer have a poor prognosis. In recent years, the development of new diagnostic techniques has enabled the identification of the main genetic alterations involved in the development of these tumours. Multiple studies have assessed the ability of certain biomarkers, such as BRCA in pancreatic cancer, IDH1 or FGFR2 in biliary tract cancer and microsatellite instability or NTRK fusions in an agnostic tumour fashion, to predict response to treatment. In this consensus, a group of experts selected by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP) reviewed the role played by these mutations in the process of carcinogenesis and their clinical implications. As a result, this article proposes a series of recommendations to optimize the determination of these biomarkers to help standardize the diagnosis and treatment of these tumours.SEOM and SEAP acknowledge the financial support for this project in the form of unrestricted collaboration in the logistics from AstraZeneca

Effects of attachment-based compassion therapy (ABCT) on brain-derived neurotrophic factor and low-grade inflammation among fibromyalgia patients: A randomized controlled trial

Fibromyalgia (FM) is a disabling syndrome characterized by chronic pain associated with fatigue. Its pathogenesis is unknown, but alterations in central sensitization, involving an imbalance of brain-derived neurotrophic factor (BDNF) and inflammatory biomarkers, appear to be implicated. The aim of this study was to evaluate the impact of attachment-based compassion therapy (ABCT) on levels of BDNF, the inflammatory markers TNF-a, IL-6, IL-10, and the C-reactive protein (CRP), analysing whether biomarkers play a mediating/moderating role in improvements in FM functional status. Thirty-four female patients with FM participated in a RCT and were assigned to ABCT or relaxation therapy. Blood extractions were conducted at baseline and post-intervention, with self-report assessments of functional status (FIQ) at baseline, post-intervention and 3-month follow-up. A pro-inflammatory composite was obtained by summing up IL-6, TNF-a and CRP normalized values. Non-parametric tests, analysis of variance and regression models were used to evaluate treatment and mediation/moderation. Compared to relaxation therapy, ABCT showed significant improvements in FIQ and decreases in BDNF, CRP, and pro-inflammatory composite. Changes in BDNF had a mediating role in FIQ. ABCT seems to reduce BDNF and appears to have anti-inflammatory effects in FM patients. Reductions in BDNF could be a mechanism of FM functional status improvement

Exploring the potential of phenolic compounds from the coffee pulp in preventing cellular oxidative stress after in vitro digestion

The coffee pulp, a by-product of the coffee industry, contains a high concentration of phenolic compounds and caffeine. Simulated gastrointestinal digestion may influence these active compounds’ bioaccessibility, bioavailability, and bioactivity. Understanding the impact of the digestive metabolism on the coffee pulp's phenolic composition and its effect on cellular oxidative stress biomarkers is essential. In this study, we evaluated the influence of in vitro gastrointestinal digestion of the coffee pulp flour (CPF) and extract (CPE) on their phenolic profile, radical scavenging capacity, cellular antioxidant activity, and cytoprotective properties in intestinal epithelial (IEC-6) and hepatic (HepG2) cells. The CPF and the CPE contained a high amount of caffeine and phenolic compounds, predominantly phenolic acids (3′,4′-dihydroxycinnamoylquinic and 3,4-dihydroxybenzoic acids) and flavonoids (3,3′,4′,5,7-pentahydroxyflavone derivatives). Simulated digestion resulted in increased antioxidant capacity, and both the CPF and the CPE demonstrated free radical scavenging abilities even after in vitro digestion. The CPF and the CPE did not induce cytotoxicity in intestinal and hepatic cells, and both matrices exhibited the ability to scavenge intracellular reactive oxygen species. The coffee pulp treatments prevented the decrease of glutathione, thiol groups, and superoxide dismutase and catalase enzymatic activities evoked by tert-butyl hydroperoxide elicitation in IEC-6 and HepG2 cells. Our findings suggest that the coffee pulp could be used as a potent food ingredient for preventing cellular oxidative stress due to its high content of antioxidant compoundsThis research was funded by the COCARDIOLAC project from the Spanish Ministry of Science and Innovation (RTI 2018-097504-B-I00) and the Excellence Line for University Teaching Staff within the Multiannual Agreement between the Community of Madrid and the UAM (2019-2023). M. Rebollo-Hernanz received funding from the FPU program of the Ministry of Universities for his predoctoral fellowship (FPU15/04238) and his grant for the requalification of the Spanish university system (CA1/RSUE/2021-00656

The Allium Derivate Propyl Propane Thiosulfinate Exerts Anti-Obesogenic Effects in a Murine Model of Diet-Induced Obesity

This study is supported by the Spanish Ministry of Science and Innovation (MICINN) (grants PID2020-119536RB-I00 and CIEN IDI-20170847). The FPU contract to R.L.-G. from Spanish Ministry of Universities (FPU 18/02026) and the contract Juan de la Cierva-Incorporacion (IJCI-2017-32485) to MO are fully acknowledge.Allium species and their organosulfur-derived compounds could prevent obesity and metabolic dysfunction, as they exhibit immunomodulatory and antimicrobial properties. Here, we report the anti-obesogenic potential and dose-dependent effects (0.1 or 1 mg/kg/day) of propyl propane thiosulfinate (PTS) in a murine model of diet-induced obesity. The obesogenic diet increased body weight gain and adipocyte size, and boosted inflammatory marker (Cd11c) expression in the adipose tissue. Conversely, PTS prevented these effects in a dose-dependent manner. Moreover, the higher dose of PTS improved glucose and hepatic homeostasis, modulated lipid metabolism, and raised markers of the thermogenic capacity of brown adipose tissue. In the colon, the obesogenic diet reduced IL-22 levels and increased gut barrier function markers (Cldn3, Muc2, Reg3g, DefaA); however, the highest PTS dose normalized all of these markers to the levels of mice fed a standard diet. Gut microbiota analyses revealed no differences in diversity indexes and only minor taxonomic changes, such as an increase in butyrate producers, Intestimonas and Alistipes, and a decrease in Bifidobacterium in mice receiving the highest PTS dose. In summary, our study provides preclinical evidence for the protective effects of PTS against obesity, which if confirmed in humans, might provide a novel plant-based dietary product to counteract this condition.Spanish GovernmentEuropean Commission PID2020-119536RB-I00 CIEN IDI-20170847Spanish Government FPU 18/02026contract Juan de la Cierva-Incorporacion IJCI-2017-3248

Assessing the sensitivity of data-limited methods for resources in the Atlantic waters

ICES Annual Science Conference 2021, online 6-10 SeptemberLength-based methods have been widely applied to estimate biological parameters and to under-stand the dynamics of marine resource populations within the category of data-limited stocksThe authors thank the financial support of the project IMPRESS (RTI2018-099868-B-I00) project, ERDF, Ministry of Science, Innovation and Universities - State Research Agency, and also of GAIN (Xunta de Galicia), GRC MERVEX (nº IN607-A 2018-4)N

Applying length-based assessment methods to fisheries resources of the Bay of Biscay and Atlantic Iberian Waters: stock status and parameters sensitivity

ASLO 2021 Aquatic Sciences Virtual Meeting, 22–27 June 2021Length-based methods have been widely applied to estimate biological parameters and to understand the dynamics of marine resource populations within the category of data-limited stocksProject IMPRESS (RTI2018-099868-B-I00), ERDF, Ministry of Science, Innovation and Universities - State Research Agency, and also of GAIN (Xunta de Galicia), GRC MERVEX (nº IN607-A 2018-4)N