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Abstract Hodgkin lymphoma (HL) represents a neoplasm primarily affecting adolescents and young adults, necessitating the development of precise diagnostic and monitoring tools. Specifically, classical Hodgkin lymphoma (cHL), comprising 90% of cases, necessitating tailored treatments to minimize late toxicities. Although positron emission tomography/computed tomography (PET/CT) has enhanced response assessment, its limitations underscore the urgency for more reliable progression predictive tools. Genomic characterisation of rare Hodgkin Reed-Sternberg (HRS) cells is challenging but essential. Recent studies employ single-cell molecular analyses, mass cytometry, and Next-Generation Sequencing (NGS) to unveil mutational landscapes. The integration of liquid biopsies, particularly circulating tumor DNA (ctDNA), extracellular vesicles (EVs), miRNAs and cytokines, emerge as groundbreaking approaches. Recent studies demonstrate ctDNA's potential in assessing therapy responses and predicting relapses in HL. Despite cHL-specific ctDNA applications being relatively unexplored, studies emphasize its value in monitoring treatment outcomes. Overall, this review underscores the imperative role of liquid biopsies in advancing HL diagnosis and monitoring.

IntroductionThe incidence of brain metastases in ovarian cancer is quite rare, being approximately 1%–2%. According to retrospective studies, patients with BRCA 1/2 mutations present a higher risk. The trimodal approach based on surgery, radiotherapy, and chemotherapy presents better outcomes, but the prognosis remains poor with overall survival since the brain progression is around 1 year. Poly-ADP-ribose polymerase inhibitors (PARPi) have provided a new alternative for the management of advanced ovarian cancer. The SOLO2, NOVA, and ARIEL3 clinical trials do not refer data on patients with brain metastases, and the published evidence for PARPi in this setting comes only from case reports and retrospective studies.Case reportWe present the case of a 54-year-old woman with stage IV ovarian high-grade serous papillary carcinoma who, after 37 months of treatment with olaparib, presented a single brain lesion. After radical treatment with surgery and adjuvant whole-brain radiotherapy, she resumed olaparib with no evidence of disease during 15 months. After a second single brain relapse treated with stereotactic radiosurgery, the patient continued olaparib beyond the brain progression with no evidence of extracranial disease. Despite that there were no changes in size or number of brain lesions, the neurological situation progressively worsened and the patient died 8 months after the second progression.DiscussionThe higher incidence of brain metastases of ovarian cancer points out a possible tropism for the CNS in BRCA-mutated patients. In preclinical studies, PARPi has shown to cross the blood–brain barrier, with possible antitumor activity in the central nervous system (CNS) while maintaining control of extracranial disease. The best survival data are obtained with a trimodal approach, and adding a PARPi could improve the survival outcomes in the context of platinum-sensitivity disease. Targeted therapies combined with local treatments are also used in other malignancies, suggesting potential effectiveness due to tumor heterogeneity. PARPi before brain metastasis may delay its diagnosis, and using iPARP after brain metastases could improve the outcome of this population.ConclusionThe role that PARPi may have in the treatment of brain metastases of ovarian cancer requires more studies. In the context of radical treatment of brain metastasis (surgery and/or RT), with no evidence of extracranial disease, maintaining treatment with PARPi beyond the brain progression should be considered.

PURPOSEData from population-based studies have shown an increased incidence of certain types of neoplasms in patients younger than 50 years (early-onset cancer [EOC]); however, little information is derived from other real-world data sources. In a nonpopulation registry, we analyzed changes in the incidence of several neoplasms in successive generations.METHODSThis cross-sectional study included all patients with a cancer diagnosis registered in one university hospital in Málaga, Spain, between 1998 and 2021, and 18 neoplasms were analyzed. For each neoplasm, the proportion of patients younger than 50 years and age 50 years and older (late-onset cancer [LOC]) of the total number of patients diagnosed each year was determined. In addition, the age limit was lowered to 45-40 years. Changes in these proportions between each year and the following year were assessed by calculating the annual percentage change (APC), and a final assessment of these changes was performed by determining the average APC (AAPC).RESULTSOf the 24,596 patients, 5,466 (22.2%) had EOC, and 19,130 (77.8%) had LOC. The incidence of all tumors increased throughout the study period in both age groups. The AAPC increase was higher in patients with EOC than in those with LOC for the following neoplasms: head and neck (6.1% v 4.6%), colon (11.0% v 8.2%), testicular (16.3% v –13.1%), non-Hodgkin lymphoma (8.4% v 5.9%), rectum (16.1% v 6.8%), kidney (27.8% v 20.1%), and sarcoma (43.4% v 28.6%). This increase was confirmed in patients younger than 45 years and 40 years.CONCLUSIONOur results are consistent with the data published for most tumor sites analyzed. This global public health problem requires the utmost attention to decrease excess cancer in young patients.

BackgroundDiffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients.Methods78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients.ResultsOur results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients.ConclusionCD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL.Clinical trial registrationhttps://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.

Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates found in sites of chronic inflammation such as tumors and autoimmune diseases. The discovery that TLS formation at tumor sites correlated with good patient prognosis has triggered extensive research into various techniques to induce their formation at the tumor microenvironment (TME). One strategy is the exogenous induction of specific cytokines and chemokine expression in murine models. However, applying such systemic chemokine expression can result in significant toxicity and damage to healthy tissues. Also, the TLS formed from exogenous chemokine induction is heterogeneous and different from the ones associated with favorable prognosis. Therefore, there is a need to optimize additional approaches like immune cell engineering with lentiviral transduction to improve the TLS formation in vivo. Similarly, the genetic and epigenetic regulation of the different phases of TLS neogenesis are still unknown. Understanding these molecular regulations could help identify novel targets to induce tissue-specific TLS in the TME. This review offers a unique insight into the molecular checkpoints of the different stages and mechanisms involved in TLS formation. This review also highlights potential epigenetic targets to induce TLS neogenesis. The review further explores epigenetic therapies (epi-therapy) and ongoing clinical trials using epi-therapy in cancers. In addition, it builds upon the current knowledge of tools to generate TLS and TLS phenotyping biomarkers with predictive and prognostic clinical potential.

Abstract Introduction Scalp cooling (SC) aims to prevent chemotherapy‐induced alopecia. The goal of this systematic review is to tackle ethical, legal, organizational and social issues related to SC. Methods A critical appraisal of the literature was carried out using a systematic review design. MEDLINE, Embase and Web of Science databases were searched up until 2 June 2021. Studies addressing these aspects in English or Spanish were considered. Representatives of both patient associations and professional scientific societies related to the topic participated in the design of the protocol and the review of the findings. Results A total of 17 studies were included. Articles were critically appraised using the MMAT and SANRA. Findings were organized into four categories: (1) ethical aspects focused on equal access, gender equity and doctor–patient communication supported by Patient Decision Aids (PtDAs); (2) patient perspective and acceptability; (3) professional perspective and acceptability; (4) organizational aspects focused on accessibility and feasibility. Conclusion Cancer patients' expectations when using SC need to be adjusted to reduce the potential distress associated with hair loss. PtDAs could help patients clarify their values and preferences regarding SC. Equal access to technology should be guaranteed. Patient or Public Contribution In this systematic review, the representatives of the patient associations (Ms. María Luz Amador Muñoz of the Spanish Association Against Cancer [AECC] and Ms. Catiana Martinez Cánovas of the Spanish Breast Cancer Federation [FECMA]) participated in the review of the study protocol, as well as in the results, discussion and conclusions, making their contributions. In the type of design of these studies (systematic reviews), it is not usual to have the direct participation of patients, but in this one, we have done so, as it is a systematic review that is part of a report of the Spanish Network of Health Technology Assessment Agencies (ETS).

Context: Prostate cancer (PCa) is the second most common type of cancer in men. Individualized risk stratification is crucial to adjust decision-making. A variety of molecular biomarkers have been developed in order to identify patients at risk of clinically significant PCa (csPCa) defined by the most common PCa risk stratification systems. Objective: The present study aims to examine the effectiveness (diagnostic accuracy) of blood or urine-based PCa biomarkers to identify patients at high risk of csPCa. Evidence acquisition: A systematic review of the literature was conducted. Medline and EMBASE were searched from inception to March 2021. Randomized or nonrandomized clinical trials, and cohort and case-control studies were eligible for inclusion. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Pooled estimates of sensitivity, specificity, and area under the curve were obtained. Evidence synthesis: Sixty-five studies (N = 34 287) were included. Not all studies included prostate-specific antigen-selected patients. The pooled data showed that the Prostate Health Index (PHI), with any cutoff point between 15 and 30, had sensitivity of 0.95–1.00 and specificity of 0.14–0.33 for csPCa detection. The pooled estimates for SelectMDx test sensitivity and specificity were 0.84 and 0.49, respectively. Conclusions: The PHI test has a high diagnostic accuracy rate for csPCa detection, and its incorporation in the diagnostic process could reduce unnecessary biopsies. However, there is a lack of evidence on patient-important outcomes and thus more research is needed. Patient summary: It has been possible to verify that the application of biomarkers could help detect prostate cancer (PCa) patients with a higher risk of poorer evolution. The Prostate Health Index shows an ability to identify 95–100 for every 100 patients suffering from clinically significant PCa who take the test, preventing unnecessary biopsies in 14–33% of men without PCa or insignificant PCa.

Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease whose prognosis is associated with clinical features, cell-of-origin and genetic aberrations. Recent integrative, multi-omic analyses had led to identifying overlapping genetic DLBCL subtypes. We used targeted massive sequencing to analyze 84 diagnostic samples from a multicenter cohort of patients with DLBCL treated with rituximab-containing therapies and a median follow-up of 6 years. The most frequently mutated genes were IGLL5 (43%), KMT2D (33.3%), CREBBP (28.6%), PIM1 (26.2%), and CARD11 (22.6%). Mutations in CD79B were associated with a higher risk of relapse after treatment, whereas patients with mutations in CD79B, ETS1, and CD58 had a significantly shorter survival. Based on the new genetic DLBCL classifications, we tested and validated a simplified method to classify samples in five genetic subtypes analyzing the mutational status of 26 genes and BCL2 and BCL6 translocations. We propose a two-step genetic DLBCL classifier (2-S), integrating the most significant features from previous algorithms, to classify the samples as N12-S, EZB2-S, MCD2-S, BN22-S, and ST22-S groups. We determined its sensitivity and specificity, compared with the other established algorithms, and evaluated its clinical impact. The results showed that ST22-S is the group with the best clinical outcome and N12-S, the more aggressive one. EZB2-S identified a subgroup with a worse prognosis among GCB-DLBLC cases.

PurposeA systematic, standardized collection of health outcomes during patient treatment and follow-up, relevant from the perspective of all stakeholders, is a crucial step toward effective and efficient disease management. This project aimed to define a standard set of health outcomes for patients with squamous cell carcinoma of the head and neck (SCCHN).MethodsThe project was led and coordinated by a scientific committee (SC). It comprised: (1) a literature review (to identify variables used during SCCHN management); (2) 1st-SC meeting (to select the variables for presentation during nominal groups-NG); (3) five NG (n=42 experts) and four interviews with patients (to reach consensus on the variables for inclusion); and (4) final-SC meeting (to review the results of NG ensuring consensus on the variables where consensus was not reached).ResultsExperts agreed to include the following variables in the standard set: treatment-related (treatment intent and type, response to treatment, treatment toxicity/complication, treatment completion), degree of health (performance status, patient-reported health status, pain, dysphonia, feeding and speech limitations, body image alteration, tracheotomy), survival (overall and progression-free survival, cause of death), nutritional (weight, nutritional intervention), other variables (smoking status, alcohol consumption, patient satisfaction with aftermath care, employment status), and case-mix variables (demographic, tumor-related, clinical and nutritional factors).ConclusionsThis project may pave the way to standardizing the collection of health outcomes in SCCHN and promote the incorporation of patients’ perspective in its management. The information provided through the systematic compilation of this standard set may define strategies to achieve high-quality, patient-centered care.

Esta investigación tiene como objetivo determinar si las empresas se hallan ante la necesidad de contar con un modelo de gestión de crisis sobre riesgos reputacionales relacionados con la desinformación mediática. Las empresas admiten encontrarse ante un nuevo riesgo corporativo y el sector profesional de la comunicación reconoce la urgencia de contar con medidas ante un evento por bulo. Para ello, se toma como punto de partida la investigación realizada a empresas españolas sobre su percepción de riesgo, donde se determinó que para el profesional los riesgos derivados de la desinformación son altamente peligrosos y se descubría la brecha entre la percepción profesional y las prioridades de la organización. El presente informe de corte cualitativo, con grupos focales a una muestra cualificada de responsables de reputación y comunicación corporativa de empresas españolas, revisa la tendencia de estas crisis y la sistemática empleada en la gestión de la crisis. Los resultados corroboran la necesidad de crear una metodología base que recoja los fundamentos sobre los que actúa la desinformación. Este hecho está dando lugar a la necesidad de ampliar el conocimiento en la creación de dinámicas eficientes para la lucha contra la desinformación. Las conclusiones bocetan un esquema metodológico que puede mejorar el trabajo de los profesionales de la comunicación.

Abstract The aim of this study is to determine the survival of patients with breast cancer treated with adjuvant chemotherapy (ACh) after the diagnosis by screening, taking comorbidity into account. This multicenter cohort study examined a population of patients taking part in four national screening programs for the early detection of breast cancer (localized or locally advanced), during the period 2000‐2008. Of the 1248 cancers detected, 266 were prevalent (21.3%), 633 were incident (50.7%), and 349 were interval (27.9%). No significant differences were detected between the three groups in terms of the distribution of comorbidity according to the CCI. After a median follow‐up of 102 months, 22.1% of the patients with interval cancer had died. The corresponding figures for the incident and prevalent cancers were 10.4% and 7.9%, respectively (P

Objetivo: Diseño y validación de un instrumento de medida de la satisfacción manifestada por pacientes en tratamiento oncológico en régimen ambulatorio en Hospital de Día. Método: Estudio transversal descriptivo de periodo mediante la administración de un cuestionario a una muestra de 148 pacientes oncológicos atendidos en régimen ambulatorio en el Hospital Costa del Sol, Marbella. Se analizaron la validez, consistencia interna, y la reproducibilidad de los items del instrumento. Resultados: La correlación ítem-escala mostró coeficientes que superaban el umbral de adecuación de 0,30. El análisis factorial de los componentes determinó un adecuado ajuste dado un valor de KMO de 0,91 y una p 0,70. El retest determinó porcentajes de acuerdo absoluto superiores al 90% en todos los ítems, y valores de kappa puntuales que oscilaban entre 0,52 y 0,93. Conclusión: Los resultados obtenidos permiten determinar que a priori el cuestionario es un instrumento fiable y válido para su utilización en lengua castellana.

Cutaneous melanoma (CM) is the most lethal form of skin cancer if it becomes metastatic, where treatment options and survival chances decrease dramatically. Immunotherapy treatments based on the immunologic checkpoint inhibitors programmed death cell protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) constituted a main breakthrough in the treatment of metastatic CM, particularly for the achievement of long-term benefits. Even though it is a very promising therapy, resistance to primary immune checkpoint blockade (ICB) arises in about 70% of CM patients treated with a CTLA-4 inhibitor, and 40–65% of CM patients administered with a PD-1-targeting treatment. Some long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are implicated in triggering pro- and anti-tumorigenic responses to various cancer treatments. The relationship between lncRNAs, circRNAs and ICB immunotherapy has not been explored in cutaneous metastatic melanoma (CMM). The aim of this pilot study is to evaluate the potential role of circRNA and lncRNA expression variability as pre-treatment predictor of the clinical response to immunotherapy in CMM patients. RNA-seq from 12 formalin-fixed paraffin-embedded (FFPE) samples from the metastatic biopsies of CMM patients treated with nivolumab was used to identify response-associated transcripts. Our findings indicate that specific lncRNAs and circRNAs, probably acting as competitive endogenous RNAs (ceRNAs), are involved in the regulatory networks of the immune response against metastatic melanoma that these patients have under treatment with nivolumab. Moreover, we established a risk score that yields predictions of the overall survival (OS) and progression-free survival (PFS) of CMM patients with high accuracy. This proof-of-principle work provides a possible insight into the function of ceRNAs, contributing to efforts to decipher the complex molecular mechanisms of ICB cancer treatment response.

Metastatic melanoma (MM) is a pathological entity with a very poor prognosis that, until a few decades ago, had a low response rate to systemic treatments. Fortunately, in the last few years, new therapies for metastatic melanoma have emerged. Currently, targeted therapy and immunotherapy are the mainstays of the therapeutic arsenal available for patients with unresectable or metastatic melanoma. However, both clinical evolution and drug efficacy in melanoma patients are very different depending on the stage at which it is diagnosed. In fact, the aggressiveness of melanoma is different depending on whether it debuts directly as metastatic disease or if what occurs is a relapse after a first diagnosis at an early stage, although the biological determinants are largely unknown. Another key aspect in the clinical management of metastatic melanoma at first diagnosis strives in the different prognosis of melanoma of unknown primary (MUP) compared to melanoma of known primary (MPK). Understanding the mechanisms behind this, and the repercussion of implementing targeted and immune therapies in this specific form is crucial for designing diagnosis and treatment decision algorithms that optimize the current strategies. In this review article, we recapitulate the information available thus far regarding the epidemiology and response to immunotherapy treatments or targeted therapy in patients diagnosed with metastatic melanoma as a first diagnosis, with especial emphasis on the emerging specific information of the subpopulation formed by MUP patients.

Background The search for immunological markers with ability of predicting clinical outcome is a priority in lymphomas, and in cancer in general. It is well known that some immunomodulatory cells, such as myeloid derived suppressor cells (MDSCs) or regulatory T cells (Tregs), are recruited by tumors, jeopardizing antitumor immunosurveillance. In this work, we have studied blood levels of these immunosuppressive cells in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), prior to and along the course of the experimental rituximab, gemcitabine, dexamethasone, and cisplatin (R2-GDP) schedule, as a translational substudy of the R2-GDP-GOTEL trial (EudraCT Number: 2014-001620-29), which included lenalidomide as an immunomodulator.Methods Blood samples were taken before treatment, at cycle 3 and end of induction. Samples were analyzed by flow cytometry. Non-parametric tests were used. Mann-Whitney U test was used to compare basal cells distributions, and Wilcoxon test was considered to compare cells distribution at different times. Spearman test was performed to measure the degree of association between cell populations.Results In this study, MDSC and Treg circulating concentration was found increased in all patients compared with a healthy control group and decreased after treatment only in patients with longest overall survival (>24 months), reaching the levels of the healthy group. Likewise, the number of inhibited T lymphocytes expressing Programmed Death-1 (PD-1) were increased in peripheral blood from patients and decreased on the treatment, whereas activated T lymphocytes increased after therapy in those with better overall survival.Conclusions In conclusion, blood concentration of MDSCs and Treg cells may be good prognostic markers for overall survival after 2 years in R/R DLBCL. These results point to a possible role of these elements in the immunosuppression of these patients, as assessed by the circulating activated and inhibited T lymphocytes, and therefore, they may be considered as therapeutic targets in DLBCL.

Squamous cell carcinoma of oral cavity (OCSCC) accounts for approximately 25% of cases of head and neck squamous cell carcinoma (HNSCC). Tobacco and alcohol consumption are the main risk factors for both cancers. Surgical resection, combined with adjuvant radiotherapy or radiochemotherapy in patients with high risk of relapse, is the key element in management in the initial stages. However, despite the availability of aggressive multidisciplinary treatments, advanced resectable OCSCC carries poor prognosis; only half of the patients are disease-free 5 years after the surgery. Immunotherapy based on the use of immune checkpoint inhibitors has been proven to be effective in a wide variety of tumours, including recurrent and metastatic HNSCC. These positive results resulted in investigations into its effectiveness in earlier stages of the disease with OCSCC emerging as an interesting research model because of the accessible location of the tumours. This article reviews the potential advantages of emerging immunotherapeutic agents [mainly monoclonal antibodies against programmed cell death-1 ( PD-1 ) immune checkpoint inhibitors] as neoadjuvant treatment for OCSCC at locoregional stages as well as the ongoing clinical trials, challenges in evaluating tumour response, and possible predictive biomarkers of response with highlights regarding the role of oral microbiota as modulators of immune response. The efficacy and safety of anti- PD-1 drugs in these patients have been proven in preliminary trials. If there is a decrease in the relapse rate and an improvement in the overall survival after surgical resection in ongoing trials, preoperative immunotherapy may be established as a treatment option for patients with early stages of the disease.

El artículo aquí presentado tiene el propósito de describir y dar a conocer el modo de proceder ante una investigación cualitativa basada en lo social haciendo uso de la narrativa como opción metodológica, la cual –más allá de explorar lo meramente objetivo– se sirva de la palabra para imaginar, representar y dar sentido a la realidad. Esta metodología se preocupa por conocer desde el interior, superando el umbral establecido por datos numéricos o estadísticos y da lugar a un extenso trayecto de investigación. Dicho camino exploratorio quedará delimitado por la voz de alguien que, en el rol de narrador e informante, debe conocer de primera mano aquella realidad que actúe como fundamento para el estudio y compartir generosamente su experiencia. Se trata de la representación subjetiva de un sujeto con base en la cual, contando como pretexto con la perspectiva anónima de quien comparte sus vocablos acerca de la temática abordada, se aspire a alcanzar y hacer más rico el saber.

Las redes sociales y la democratización de la moda han impactado en las estrategias comunicativas del sector del lujo. Este artículo realiza un análisis descriptivo a través del análisis de contenido de todos los vídeos alojados —4079— en los canales de YouTube de las 12 principales marcas de moda de lujo. El principal objetivo es conocer la evolución de los contenidos audiovisuales de las principales marcas de moda de lujo en YouTube e identificar los principales formatos utilizados. Los resultados aportan una clasificación de los principales formatos utilizados por el sector del lujo, así como su capacidad de interacción. La investigación concluye que las marcas de moda de lujo usan más formatos convencionales que estrategias de contenido asociadas al branded content. Del mismo modo, se aprecia que las marcas de moda de lujo apenas interaccionan con su público objetivo.

Targeted therapy in metastatic melanoma often achieves a major tumour regression response and significant long-term survival via the release of antigens that reinduce immunocompetence. The biomarkers thus activated may guide the prediction of response, but this association and its mechanism have yet to be established. Blood samples were collected from nineteen consecutive patients with metastatic melanoma before, during, and after treatment with targeted therapy. Differential gene expression analysis was performed, which identified the genes involved in the treatment, both in the first evaluation of response and during progression. Although clinical characteristics of the patients were poorer than those obtained in pivotal studies, radiological responses were similar to those reported previously (objective response rate: 73.7%). In the first tumour assessment, the expression of some genes increased (CXCL-10, SERPING1, PDL1, and PDL2), while that of others decreased (ARG1, IL18R1, IL18RAP, IL1R1, ILR2, FLT3, SLC11A1, CD163, and S100A12). The analysis of gene expression in blood shows that some are activated and others inhibited by targeted therapy. This response pattern may provide biomarkers of the immune reinduction response, which could be used to study potential combination treatments. Nevertheless, further studies are needed to validate these results.

Oral squamous cell carcinoma (OSCC) constitutes approximately 25% of all head and neck cancer, for which the consumption of tobacco and alcohol are the main associated risk factors. The field cancerization effect of OSCC is one of the main reasons for the poor survival rates associated with this disease. Despite some advances, its ccharacterization and early diagnosis continue to challenge modern oncology, and the goal of improving the prognosis remains to be achieved. Among new early diagnostic tools for OSCC that have been proposed, liquid biopsy appears to be an ideal candidate, as studies have shown that the analysis of blood and saliva provides promising data for the early detection of relapses or second tumours.

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth cancer on incidence worldwide. Tobacco and alcohol consumption are the most classical risk factors associated with its development. Autophagy process has a dual effect both in tumourigenesis and tumour suppressing activity. To investigate the importance of this pathway in HNSCC susceptibility, a risk factor matched case-control association study was performed with four candidate polymorphisms in autophagy genes (ATG2B, ATG5, ATG10, ATG16L1). We found an association between the variant in ATG10 rs1864183 and a higher susceptibility to develop laryngeal cancer, ATG2B rs3759601 and pharyngeal cancer and ATG16L1 rs2241880 and oral carcinoma. ATG5 rs2245214 SNP was not associated with any location. Overall, our results indicate the importance of the autophagy pathway in the susceptibility of head and neck squamous cell carcinoma and demonstrate the heterogeneity between its locations encompassed under a single terminology.

The main obstacle for designing effective treatment approaches in breast cancer is the extensive and the characteristic heterogeneity of this tumor. The vast majority of critical genomic changes occurs during breast cancer progression, creating a significant variability within primary tumors as well as between the primary breast cancer and their metastases, a hypothesis have already demonstrated in retrospective studies (1). A clear example of this is the HER2-positive breast cancer. In these tumors, we can find all of the transcriptional subtypes of breast cancer, even the basal like or luminal A subtypes. Although the HER2-enriched is the most representative transcriptional subtype in the HER2-positive breast cancer, we can find it too in breast cancers with HER2-negative status. This intrinsic subtype shows a high expression of the HER2 and is associated with proliferation-related genes clusters, among other features. Therefore, two hypotheses can be suggested. First, the HER2 amplification can be a well-defined driver event present in all of the intrinsic subtypes, and not a subtype marker isolated. Secondly, HER2-enriched subtype can have a distinctive transcriptional landscape independent of HER2 amplification. In this review, we present an extensive revision about the last highlights and advances in clinical and genomic settings of the HER2-positive breast cancer and the HER2-enriched subtype, in an attempt to improving the knowledge of the underlying biology of both entities and to explaining the intrinsic heterogeneity of HER2-positive breast cancers.

We investigate the clinical and pathological features related to variations in colorectal tumour apoptosis, proliferation and angiogenesis and the influence of the latter in short-term mortality (2 years); 551 tumour samples from a prospective cohort of patients with colorectal cancer were examined and tumour biology markers were determined as follows: percentage of apoptotic cells, by the terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling technique; Ki-67 antigen, as a cell proliferation marker and density of microvessels (as a marker of angiogenesis). An increase in the percentage of cellular apoptosis is significantly related to the presence of poorly differentiated tumours, with vascular invasion (p

Follicular lymphoma (FL) is an indolent but largely incurable disease. Some patients suffer histological transformation to a more aggressive subtype with poorer prognosis. This study aimed to improve our understanding of the genetics underlying FL histological transformation, and to identify genetic drivers or promoters of the transformation by elucidating the differences between FL samples from patients who did and did not transform. We conducted targeted massive parallel sequencing of 22 pre-transformed FL/transformed diffuse large B-cell lymphoma pairs and 20 diagnostic samples from non-transformed FL patients. Additionally, 22 matched samples from 11 transformed FL patients (pre-transformed FL and diffuse large B-cell lymphoma) and 9 non-transformed FLs were studied for copy number variation using SNP arrays. We identified recurrently mutated genes that were enriched at transformation, most notably LRP1B, GNA13 and POU2AF1, which have roles in B-cell differentiation, GC architecture and migration. Mutations in POU2AF1 might be associated with lower levels of expression, were more frequent in transformed FLs, and seemed to be specific to transformed- compared with de novo-diffuse large B-cell lymphomas. Pre-transformed FLs carried more mutations per sample and had greater subclonal heterogeneity than non-transformed FLs. Finally, we identified four mutated genes in FL samples that differed between patients who did and did not transform: NOTCH2, DTX1, UBE2A and HIST1H1E. The presence of mutations in these genes was associated with shorter time to transformation when mutated in the FL biopsies. This information might be useful for identifying patients at higher risk of transformation.

Long non-coding RNAs are increasingly recognised to be important factors in regulating cellular processes and comprise a large faction of the transcriptome, however most are uncharacterised. Here the authors present RACE-Seq, a tool to improve and extend the annotation of low-expression transcripts.

Intravenous rituximab plus chemotherapy is standard treatment for diffuse large B-cell lymphoma. A subcutaneous formulation of rituximab is expected to simplify and shorten drug preparation and administration, and to reduce treatment burden. MabEase (clinicaltrials.gov Identifier: 01649856) examined efficacy, safety and patient satisfaction with subcutaneous rituximab plus chemotherapy in treatment-naïve patients with diffuse large B-cell lymphoma. Patients were randomized 2:1 to subcutaneous rituximab (intravenous 375 mg/m2 cycle 1; subcutaneous 1,400 mg cycles 2–8) or intravenous rituximab (375 mg/m2 cycles 1–8) plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 14 or 21 days. The primary endpoint was investigator-assessed complete response/unconfirmed complete response. Secondary endpoints included safety, treatment satisfaction (Cancer Treatment Satisfaction Questionnaire and Rituximab Administration Satisfaction Questionnaire), time savings, and survival. Of 576 randomized patients, 572 (378 subcutaneous; 194 intravenous) received treatment. End of induction complete response/unconfirmed complete response rates were 50.6% (subcutaneous) and 42.4% (intravenous). After a median 35 months, median overall, event-free and progression-free survivals were not reached. Grade ≥3 adverse events (subcutaneous 58.3%; intravenous 54.3%) and administration-related adverse events (both groups 21%) were similar between arms. Injection-site reactions were more common with subcutaneous injections (5.7% versus 0%, respectively). Rituximab Administration Satisfaction Questionnaire scores for ‘impact on activities of daily living’, ‘convenience’, and ‘satisfaction’ were improved with subcutaneous versus intravenous injections; Cancer Therapy Satisfaction Questionnaire scores were similar between arms. Median administration time (6 minutes vs. 2.6 to 3.0 hours), chair/bed and overall hospital times were shorter with subcutaneous versus intravenous rituximab. Overall, subcutaneous and intravenous rituximab had similar efficacy and safety, with improved patient satisfaction and time savings.

BACKGROUND:Follicular lymphoma is the second most common non-Hodgkin lymphoma in the United States and Europe. However, most of the prospective randomized studies have very little follow-up compared to the long natural history of the disease. The primary aim of this study was to investigate the long-term survival of our series of patients with follicular lymphoma. PATIENTS AND METHODS:A total of 1074 patients with newly diagnosed FL were enrolled. Patients diagnosed were prospectively enrolled from 1980 to 2013. RESULTS:Median follow-up was 54.9 months and median overall survival is over 20 years in our series. We analyzed the patients who are still alive beyond 10 years from diagnosis in order to fully assess the prognostic factors that condition this group. Out of 166 patients who are still alive after more than 10 years of follow-up, 118 of them (73%) are free of evident clinical disease. Variables significantly associated with survival at 10 years were stage < II (p

Rueda Monroy, J. A. (2024). Los incesantes desafíos de la discapacidad en el derecho sociolaboral: algunas reflexiones sobre cuestiones actuales. Revista Española de Discapacidad, 12(2), 217-227.

Este artículo analiza de manera integrada los antecedentes y las implicaciones, para los resultados empresariales, del desarrollo de estrategias medioambientalmente proactivas en las organizaciones. Específicamente, estudia la influencia que las presiones de los clientes —legales, competitivas y éticas— tienen en el desarrollo de estas prácticas, y cómo esa proactividad repercute en los resultados económicos y medioambientales. Para alcanzar los objetivos planteados se utiliza la metodología de las ecuaciones estructurales en una muestra de 361 empresas españolas del sector secundario. Los resultados revelan que la presión de los clientes, las motivaciones competitivas y el compromiso de los directivos con el medio ambiente explican el porqué de las estrategias proactivas, mientras que no puede afirmarse que la legislación medioambiental del sector incentive su puesta en marcha. Por su parte, se constata un efecto positivo de estas estrategias en el desempeño económico y medioambiental, lo cual contribuye a disipar las dudas existentes en la literatura en torno a la naturaleza y signo de esas relaciones.

Fundamentos: El tratamiento de mantenimiento con rituximab del linfoma folicular (LF) que responde a la inducción en primera línea, aumenta de manera significativa la supervivencia libre de progresión en comparación con la observación. Para evaluar económicamente esta opción terapéutica, se realizó un análisis de coste-efectividad del tratamiento de mantenimiento del LF tras la inducción en primera línea con rituximab frente a la observación de la enfermedad. Métodos: Se hizo un modelo de Markov del LF, con cuatro estados de salud (supervivencia libre de progresión en primera o segunda línea, progresión y muerte). Las probabilidades de transición entre los estados se obtuvieron de los ensayos clínicos PRIMA y EORTC 20981. Las utilidades de los estados se obtuvieron de la bibliografía. El uso de recursos sanitarios, desde la perspectiva del Sistema Nacional de Salud, fue estimado por un panel de expertos clínicos españoles. Los costes unitarios (¿ del año 2011) se obtuvieron de fuentes españolas. Se efectuaron análisis determinísticos y probabilísticos. Resultados: En el caso base del análisis determinístico, para un horizonte temporal de 30 años, el coste por año de vida ganado (AVG) y por año de vida ajustado por calidad (AVAC) ganado, fue de 5.663 E y 6.253 E, respectivamente. Los análisis de sensibilidad confirmaron la estabilidad del caso base para horizontes temporales de 10 y 20 años y diversas distribuciones estadísticas (Weibull, exponencial, log-logística, log-normal, Gompertz y gamma) oscilando entre 4.222 y 8.766 E. El mantenimiento con rituximab es coste-efectivo a partir de un horizonte temporal de 5,7 años (coste por AVAC ganado de 29.998 E). Conclusión: En comparación con la observación, el tratamiento de mantenimiento con rituximab del LF que responde a la inducción en primera línea, es coste-efectivo de acuerdo con el presente modelo.

We investigate the properties of a Block Decomposition Method (BDM), which extends the power of a Coding Theorem Method (CTM) that approximates local estimations of algorithmic complexity based on Solomonoff–Levin’s theory of algorithmic probability providing a closer connection to algorithmic complexity than previous attempts based on statistical regularities such as popular lossless compression schemes. The strategy behind BDM is to find small computer programs that produce the components of a larger, decomposed object. The set of short computer programs can then be artfully arranged in sequence so as to produce the original object. We show that the method provides efficient estimations of algorithmic complexity but that it performs like Shannon entropy when it loses accuracy. We estimate errors and study the behaviour of BDM for different boundary conditions, all of which are compared and assessed in detail. The measure may be adapted for use with more multi-dimensional objects than strings, objects such as arrays and tensors. To test the measure we demonstrate the power of CTM on low algorithmic-randomness objects that are assigned maximal entropy (e.g., π ) but whose numerical approximations are closer to the theoretical low algorithmic-randomness expectation. We also test the measure on larger objects including dual, isomorphic and cospectral graphs for which we know that algorithmic randomness is low. We also release implementations of the methods in most major programming languages—Wolfram Language (Mathematica), Matlab, R, Perl, Python, Pascal, C++, and Haskell—and an online algorithmic complexity calculator.

Whole genome methylation profiling at a single cytosine resolution is now feasible due to the advent of high-throughput sequencing techniques together with bisulfite treatment of the DNA. To obtain the methylation value of each individual cytosine, the bisulfite-treated sequence reads are first aligned to a reference genome, and then the profiling of the methylation levels is done from the alignments. A huge effort has been made to quickly and correctly align the reads and many different algorithms and programs to do this have been created. However, the second step is just as crucial and non-trivial, but much less attention has been paid to the final inference of the methylation states. Important error sources do exist, such as sequencing errors, bisulfite failure, clonal reads, and single nucleotide variants. We developed MethylExtract, a user friendly tool to: i) generate high quality, whole genome methylation maps and ii) detect sequence variation within the same sample preparation. The program is implemented into a single script and takes into account all major error sources. MethylExtract detects variation (SNVs – Single Nucleotide Variants) in a similar way to VarScan, a very sensitive method extensively used in SNV and genotype calling based on non-bisulfite-treated reads. The usefulness of MethylExtract is shown by means of extensive benchmarking based on artificial bisulfite-treated reads and a comparison to a recently published method, called Bis-SNP. MethylExtract is able to detect SNVs within High-Throughput Sequencing experiments of bisulfite treated DNA at the same time as it generates high quality methylation maps. This simultaneous detection of DNA methylation and sequence variation is crucial for many downstream analyses, for example when deciphering the impact of SNVs on differential methylation. An exclusive feature of MethylExtract, in comparison with existing software, is the possibility to assess the bisulfite failure in a statistical way. The source code, tutorial and artificial bisulfite datasets are available at http://bioinfo2.ugr.es/MethylExtract/ and http://sourceforge.net/projects/methylextract/, and also permanently accessible from 10.5281/zenodo.7144.

Whole genome methylation profiling at a single cytosine resolution is now feasible due to the advent of high-throughput sequencing techniques together with bisulfite treatment of the DNA. To obtain the methylation value of each individual cytosine, the bisulfite-treated sequence reads are first aligned to a reference genome, and then the profiling of the methylation levels is done from the alignments. A huge effort has been made to quickly and correctly align the reads and many different algorithms and programs to do this have been created. However, the second step is just as crucial and non-trivial, but much less attention has been paid to the final inference of the methylation states. Important error sources do exist, such as sequencing errors, bisulfite failure, clonal reads, and single nucleotide variants. We developed MethylExtract, a user friendly tool to: i) generate high quality, whole genome methylation maps and ii) detect sequence variation within the same sample preparation. The program is implemented into a single script and takes into account all major error sources. MethylExtract detects variation (SNVs – Single Nucleotide Variants) in a similar way to VarScan, a very sensitive method extensively used in SNV and genotype calling based on non-bisulfite-treated reads. The usefulness of MethylExtract is shown by means of extensive benchmarking based on artificial bisulfite-treated reads and a comparison to a recently published method, called Bis-SNP. MethylExtract is able to detect SNVs within High-Throughput Sequencing experiments of bisulfite treated DNA at the same time as it generates high quality methylation maps. This simultaneous detection of DNA methylation and sequence variation is crucial for many downstream analyses, for example when deciphering the impact of SNVs on differential methylation. An exclusive feature of MethylExtract, in comparison with existing software, is the possibility to assess the bisulfite failure in a statistical way. The source code, tutorial and artificial bisulfite datasets are available at http://bioinfo2.ugr.es/MethylExtract/ and http://sourceforge.net/projects/methylextract/, and also permanently accessible from 10.5281/zenodo.7144.

BACKGROUND: We studied anomalous extracellular mRNAs in plasma from patients with diffuse large B-cell lymphoma (DLBCL) and their survival implications. mRNAs studied have been reported in the literature as markers of poor (BCL2, CCND2, MYC) and favorable outcome (LMO2, BCL6, FN1) in tumors. These markers were also analyzed in lymphoma tissues to test possible associations with their presence in plasma. METHODOLOGY/PRINCIPAL FINDINGS: mRNA from 42 plasma samples and 12 tumors from patients with DLBCL was analyzed by real-time PCR. Samples post-treatment were studied. The immunohistochemistry of BCL2 and BCL6 was defined. Presence of circulating tumor cells was determined by analyzing the clonality of the immunoglobulin heavy-chain genes by PCR. In DLBCL, MYC mRNA was associated with short overall survival. mRNA targets with unfavorable outcome in tumors were associated with characteristics indicative of poor prognosis, with partial treatment response and with short progression-free survival in patients with complete response. In patients with low IPI score, unfavorable mRNA targets were related to shorter overall survival, partial response, high LDH levels and death. mRNA disappeared in post-treatment samples of patients with complete response, and persisted in those with partial response or death. No associations were found between circulating tumor cells and plasma mRNA. Absence of BCL6 protein in tumors was associated with presence of unfavorable plasma mRNA. CONCLUSIONS/SIGNIFICANCE: Through a non-invasive procedure, tumor-derived mRNAs can be obtained in plasma. mRNA detected in plasma did not proceed from circulating tumor cells. In our study, unfavorable targets in plasma were associated with poor prognosis in B-cell lymphomas, mainly MYC mRNA. Moreover, the unfavorable targets in plasma could help us to classify patients with poor outcome within the good prognosis group according to IPI.

Prostatitis "La prostatitis es siempre o casi siempre de origen infeccioso, y reconoce por causa la acción de un microbio sobre un terreno preparado". Legueu. (1). Puede la próstata ser infectada por muchas vías y por muchos microbios: De hecho hay autores como Keyes (2) que consideran que la próstata de un adulto, no puede garantizarse como libre de una infección crónica silenciosa de la misma manera que no puede serlo una amígdala.