Topological regulation of the estrogen transcriptional response by ZATT-mediated inhibition of TOP2B activity.

Human type-II topoisomerases, TOP2A and TOP2B, remove transcription associated DNA supercoiling, thereby affecting gene-expression programs, and have recently been associated with 3D genome architecture. Here, we study the regulatory roles of TOP2 paralogs in response to estrogen, which triggers an acute transcriptional induction that involves rewiring of genome organization. We find that, whereas TOP2A facilitates transcription, as expected for a topoisomerase, TOP2B limits the estrogen response. Consistent with this, TOP2B activity is locally downregulated upon estrogen treatment to favor the establishment and stabilization of regulatory chromatin contacts, likely through an accumulation of DNA supercoiling. We show that estrogen-mediated inhibition of TOP2B requires estrogen receptor α (ERα), a non-catalytic function of TOP2A, and the action of the atypical SUMO-ligase ZATT. This mechanism of topological transcriptional-control, which may be shared by additional gene-expression circuits, highlights the relevance of DNA topoisomerases as central actors of genome dynamics.

Assessment of an intervention for preventing pediatric overweight and obesity through the World Café technique: A qualitative study.

PURPOSE: To evaluate the self-reported perspectives of participants involved in the Previene Cádiz intervention for preventing pediatric overweight and obesity. DESIGN AND METHODS: This qualitative study collected information through the World Café technique. A purposive sample of 40 participants was used, of which 14 were schoolchildren, 12 were teachers, and 14 were parent volunteers. The data were segmented, and concepts were created and grouped into dimensions and categories. RESULTS: The participants confirmed they had learned new information and behaviors about healthy habits. Parental awareness was considered a crucial and necessary element in changing family habits; therefore, increasing the motivation of family members was deemed a critical task in public health interventions conducted in school settings. DISCUSSION: Despite the suitability of qualitative methodology to evaluate the perceptions of the main players in an educational intervention, scientific literature is scarce. Obtaining information from the educational community about an intervention is not always easy, so the perspectives of teachers, students, and families about the Previene Cádiz intervention through the World Café approach is considered a relevant contribution. CONCLUSIONS: The participants considered the intervention positive in terms of learning and fostering increased knowledge, awareness, and healthy behaviors. PRACTICE IMPLICATIONS: Future interventions should encourage the active participation of all social groups involved, integrating dynamic and collaborative training activities that are acceptable to all participants.

Immune defects associated with lower SARS-CoV-2 BNT162b2 mRNA vaccine response in aged people.

The immune factors associated with impaired SARS-CoV-2 vaccine response in elderly people are mostly unknown. We studied individuals older than 60 and younger than 60 years, who had been vaccinated with SARS-CoV-2 BNT162b2 mRNA, before and after the first and second dose. Aging was associated with a lower anti-RBD IgG levels and a decreased magnitude and polyfunctionality of SARS-CoV-2-specific T cell response. The dramatic decrease in thymic function in people > 60 years, which fueled alteration in T cell homeostasis, and their lower CD161+ T cell levels were associated with decreased T cell response 2 months after vaccination. Additionally, deficient DC homing, activation, and TLR-mediated function, along with a proinflammatory functional profile in monocytes, were observed in the > 60-year-old group, which was also related to lower specific T cell response after vaccination. These findings might be relevant for the improvement of the current vaccination strategies and for the development of new vaccine prototypes.

Aplicación del grupoanálisis en la práctica clínica comunitaria / Application of group analysis in the community-based clinical practice

El grupoanálisis nació tras una primera experiencia de análisis mutuo (T. Burrow) retomada por Foulkes como experiencia psicoterapéutica grupal. Integra aspectos sociológicos (Elias), psicoanalíticos (M. Klein, A. Freud, Jung), y más recientemente de la teoría del apego (Bowlby, Marrone) y las neurociencias (Golstein, Siegel). Es un modelo de pensamiento que se adapta a las diversas psicopatologías y encuadres asistenciales basado en el análisis de los componentes del grupo realizado por todos sus miembros, incluido el profesional. En este artículo se analizan algunos elementos conceptuales y clínicos que constituyen la estructura conceptual de un modelo introducido en España en 1976 (Campos, Guimón) mediante los cursos formativos de la Universidad de Deusto —Fundación OMIE. Es un modelo que se utiliza en diversos recursos de la amplia red comunitaria en la que se inserta la salud mental, considerando a pacientes, a sus familiares y a los profesionales como actores básicos de una red interpersonal de influencias mutuas. (AU)

Group analysis was born after a first experience of mutual analysis (T. Burrow) taken up by Foulkes as a group psychotherapeutic experience. It integrates sociological (Elias) and psychoanalytical (M. Klein, A. Freud, Jung) aspects, and more recently some elements of attachment theory (Bowlby, Marrone) and neuroscience (Golstein, Siegel). It is a model of thought that adjusts to various psychopathologies and care settings based on the analysis of the group carried out by all its members, professionals included. In this article some of the conceptual and clinical elements of a model introduced in Spain in 1976 by Campos and Guimón through training courses in the University of Deusto—OMIE Foundation are analyzed. It is a model that is used in various resources of the wide community network in which mental health is inserted, considering patients, families, and professionals as basic actors in an interpersonal network of mutual influences. (AU)

Light regulates the degradation of the regulatory protein VE-1 in the fungus Neurospora crassa.

BACKGROUND: Fungi use light as an environmental signal to regulate developmental transitions that are key aspects of their biological cycles and that are also relevant for their dispersal and infectivity as plant or animal pathogens. In addition, light regulates the accumulation of photoprotective pigments, like carotenoids, and other secondary metabolites. Most fungal light responses occur after changes in gene transcription and we describe here a novel effect of light in the regulation of degradation of VE-1, a key component of the velvet complex, in the model fungus Neurospora crassa. The velvet complex is a fungal-specific protein complex that coordinates fungal development, secondary metabolism, and light regulation by interacting with other regulators and photoreceptors and modifying gene expression. RESULTS: We have characterized the role of VE-1 during conidiation in N. crassa. In vegetative mycelia, VE-1 is localized in the cytoplasm and nuclei and is required for light-dependent transcription but does not interact with the photoreceptor and transcription factor WC-1. VE-1 is more stable in light than in darkness during asexual development (conidiation). We have shown that this light effect requires the blue-light photoreceptor WC-1. We have characterized the role of the proteasome, the COP9 signalosome (CSN), and the adaptor component of cullin-RING ubiquitin ligases, FWD-1, in the degradation of VE-1. CONCLUSIONS: We propose that this new effect of light allows the fungal cell to adapt quickly to changes in light exposure by promoting the accumulation of VE-1 for the regulation of genes that participate in the biosynthesis of photoprotective pigments.

Teletherapy and hospitalizations in patients with serious mental illness during the COVID-19 pandemic: A retrospective multicenter study.

BACKGROUND: Interventions with patients with Serious Mental Illness (SMI) had to adapt rapidly to the COVID-19 safety restrictive measures, leading to the widespread use of teletherapy as an alternative. OBJECTIVES: The aims of this study were to compare the use of different intervention modalities with patients with SMI during the first wave of the pandemic and examine their association with emergency hospital visits and hospitalization rates six months later. METHODS: Records of 270 service users of fifteen outpatient mental health services across Spain, were retrospectively assessed. We retrieved clinical data and data on the modality of intervention received (in-person, over the phone, videoconferencing) in three time points (before, during and after the first COVID-19 wave). Also, data were retrieved regarding the frequency of their emergency hospital visits and hospitalization rates, two, four and six months later. RESULTS: During the first wave of the pandemic, teletherapy (over the phone and videoconferencing) was the modality most widely used, whilst in-person therapy sessions were significantly reduced, though they seemed to return to pre-COVID levels after the first wave had passed. Importantly, patients receiving teletherapy during the first wave seemed to have significantly fewer emergency visits and hospitalization rates four and six months later (χ2 = 13.064; p < .001). Multilevel analyses revealed that patients receiving videoconferencing interventions had fewer hospitalizations six months after the first wave (OR = 0.25; p = .012). CONCLUSIONS: Under challenging circumstances as those created by the COVID pandemic, teletherapy is a useful tool for protection against hospitalizations and can be used as an alternative to in-person therapy, to ensure continuity of care for patients with SMI.

Independent and Combined Association of Lifestyle Behaviours and Physical Fitness with Body Weight Status in Schoolchildren.

(1) Background: Lifestyle behaviours and physical fitness play a critical role in the development of childhood obesity. It has been demonstrated in this study that self-reported physical fitness is representative of a healthy lifestyle and thus is associated with a lower incidence of overweight/obesity. The objective of this study was to analyse the independent and combined association of lifestyles (physical activity, screen time, diet and hours of sleep) and self-reported physical fitness with body weight in schoolchildren. (2) Methods: This study performed a descriptive and cross-sectional analysis. The study sample consisted of 864 schoolchildren between 8−9 years old from 26 schools of the province of Cádiz. To measure lifestyles and self-reported physical fitness, questionnaires were administered to both schoolchildren and families. To obtain the body weight status, the children were measured by body mass index (BMI). To verify the influence of lifestyles and self-reported physical fitness on the body weight status of schoolchildren, a combined score of lifestyles and self-reported physical fitness was calculated. (3) Results: Schoolchildren who followed healthier lifestyles and presented good physical fitness had a better body weight status (p < 0.001). Schoolchildren who had less healthful lifestyles and bad physical fitness had a 10.34 times higher risk of being overweight or obese (p = 0.004). (4) Conclusions: It has been shown that there is an independent and combined association between lifestyles and physical fitness on the body weight of the schoolchildren. We have suggested strategies to get children to adopt healthy lifestyles and good physical fitness to maintain a healthy body weight and prevent obesity.

Mesenchymal Stromal Cells for Treating Steroid-Resistant Acute and Chronic Graft Versus Host Disease: A Multicenter Compassionate Use Experience.

Graft versus host disease (GVHD) is a severe complication after allogenic hematopoietic cell transplantation (HSCT). Several clinical trials have reported the use of mesenchymal stromal cells (MSCs) for the treatment of GVHD. In March 2008, the Andalusian Health Care System launched a compassionate use program to treat steroid-resistant GVHD with MSC. Clinical-grade MSC were obtained under GMP conditions. MSC therapy was administered intravenously in four separate doses of 1 × 106 cells/kg. Sixty-two patients, 45 males (7 children) and 17 females (2 children), received the treatment. Patients had a median age of 39 years (range: 7-66) at the time of the allogenic HSCT. The overall response was achieved in 58.7% of patients with acute (a)GVHD. Two years' survival for aGVHD responders was 51.85%. The overall response for patients with chronic (c)GVHD was 65.50% and the 2-year survival rate for responders was 70%. Age at the time of HSCT was the only predictor found to be inversely correlated with survival in aGVHD. Regarding safety, four adverse events were reported, all recovered without sequelae. Thus, analysis of this compassionate use experience shows MSC to be an effective and safe therapeutic option for treating refractory GVHD, resulting in a significant proportion of patients responding to the therapy.

Machine learning and network medicine approaches for drug repositioning for COVID-19.

We present two machine learning approaches for drug repurposing. While we have developed them for COVID-19, they are disease-agnostic. The two methodologies are complementary, targeting SARS-CoV-2 and host factors, respectively. Our first approach consists of a matrix factorization algorithm to rank broad-spectrum antivirals. Our second approach, based on network medicine, uses graph kernels to rank drugs according to the perturbation they induce on a subnetwork of the human interactome that is crucial for SARS-CoV-2 infection/replication. Our experiments show that our top predicted broad-spectrum antivirals include drugs indicated for compassionate use in COVID-19 patients; and that the ranking obtained by our kernel-based approach aligns with experimental data. Finally, we present the COVID-19 repositioning explorer (CoREx), an interactive online tool to explore the interplay between drugs and SARS-CoV-2 host proteins in the context of biological networks, protein function, drug clinical use, and Connectivity Map. CoREx is freely available at: https://paccanarolab.org/corex/.

BENEFIT AND SAFETY OF INCOBOTULINUMTOXINA FOR EARLY MANAGEMENT OF POST-STROKE SPASTICITY IN A PATIENT WITH SARS-COV-2: A CASE REPORT.

OBJECTIVE: To describe a case of early management of post-stroke spasticity treated with incobotulinumtoxinA (IncoA) in a patient with SARS-CoV-2 (COVID-19). Scarce information is available on this subject, as the COVID-19 pandemic has necessitated postponement of interventions in infected and clinically suspicious patients. CASE REPORT: A 58-year-old woman presenting with ischaemic stroke, was infected with SARS-CoV-2 virus due to nosocomial contact. Despite clinical improvement, the patient developed early spasticity. Modified Ashworth Scale (MAS) was grade II in her left elbow, wrist flexors and left gastrocnemius. IncoA was injected, using ultrasound guidance, in her upper and lower limbs. No complications were reported after the procedure. Two weeks afterwards, there was an improvement in her motor balance and spasticity, MAS was graded I in the left elbow, wrist flexors, and II in the left gastrocnemius. At 12 weeks, the patient reported improvement at a global level, with increasing independence and functionality. CONCLUSION: This case indicates the benefits and safety of IncoA for early treatment of post-stroke spasticity in a patient with confirmed SARS-CoV-2. Despite the current status of national healthcare systems due to the COVID-19 pandemic, increased efforts should be made to avoid discontinuation of treatment for spasticity.

Retirada accidental de sondas enterales en el paciente crítico / Accidental removal of feeding tubes in critical patients

Objetivo: evaluar el impacto de una sesión formativa en las tasas de retirada accidental (RA) [autorretirada y retirada por causa externa al paciente (CEP)] de la sonda enteral (SE) y en los niveles de analgosedación e identificación del delirio, en pacientes de un Servicio de Cuidados Intensivos y Grandes Quemados (UCI-UGQ).Método: estudio observacional prospectivo antes-después, realizado en una UCI-UGQ de 24 camas. Primer periodo: del 15-10-2018 al 15-01-2019, segundo periodo: del 15-07-2019 al 15-01-2020. Entre periodos se comunicaron los resultados y se hizo una sesión formativa (sujeción SE, valoración dolor, sedación y delirio). Incluidos todos los pacientes portadores de SE. Variables: demográficas, gravedad, motivo de retirada, evento adverso como consecuencia de la retirada o reinserción, dolor, sedación/agitación y delirio. Análisis: descriptivo y tasas de incidencia por 1.000 días dispositivo. Aprobado por CEIm.Resultados: ingresos en 2018 vs. 2019: 232 vs. 408 (1.586 vs. 3.149 días estancia); mujeres: 34% vs. 42%. SAPS III, Mediana (RIC): 57 (45-67) vs. 45 (33-54). Insertadas 156 vs. 295 SE. Tasas de RA por 1.000 días de dispositivo: global 56,68 vs. 45,87 (p= 0,42); autorretirada 48,13 vs. 37,72 (p= 0,36), CEP 8,56 vs. 8,15 (p= 0,90). No se registraron eventos adversos. En el momento de la autorretirada presentaban dolor (EVN/ESCID> 0) 26,6% vs. 19% pacientes; agitación (RASS> 0) 66,6% vs. 40,6% pacientes; delirio (CAM-ICU positivo) 33,3% vs. 20,3% pacientes.Conclusiones: tras la sesión formativa se observó una reducción no significativa en las tasas de RA. En las autorretiradas se comprobó un descenso significativo de la agitación y un descenso clínicamente relevante del dolor y presencia de delirio.(AU)

Objective: to assess the impact of a training session on accidental removal (AR) rates of the feeding tube (FT) [self-removal and removal due to a cause external to the patient (CEP] and on the levels of analgesia & sedation and delirium detection, in patients from an Intensive Care and Major Burns Unit (ICU-MBU).Method: an observational, before-and-after, prospective study, conducted in a 24-bed ICU-MBU- First period: October, 15th, 2018 to January, 15th, 2019: second period: July, 15th, 2019 to January, 15th, 2020. Results were reported between periods, and a training session was conducted (FT attachment, pain assessment, sedation, and delirium). All patients with FT were included. Variables: demographics, severity, reason for removal, adverse event as a consequence of removal or reinsertion, pain, sedation/agitation, and delirium. Analysis: descriptive, and incidence rates per 1,000 device days. Approved by the Drug Research Ethics Committee (CEIm).Results: hospitalizations in 2018 vs. 2019: 232 vs. 408 (1,586 vs. 3,149 hospitalization days); women: 34% vs. 42%. SAPS III, Median (IQR): 57 (45-67) vs. 45 (33-54). FTs inserted: 156 vs. 295. AR rates per 1,000 device days: overall 56.68 vs. 45.87 (p= 0.42); self-removal: 48.13 vs. 37.72 (p= 0.36), CEP 8.56 vs. 8.15 (p= 0.90). No adverse events were reported. At the time of self-removal, 26.6% vs. 19% patients presented pain (VAS/ESCID> 0); 66.6% vs. 40.6% patients presented agitation (RASS> 0, and 33.3% vs. 20.3% patients presented delirium (positive CAM-ICU).Conclusions: after the training session, a non-significant reduction in AR rates was observed. In cases of self-removal, a significant reduction in agitation was observed, as well as a clinically relevant reduction in pain and presence of delirium.(AU)

A Multimodal Intervention for Prevention of Overweight and Obesity in Schoolchildren. A Protocol Study "PREVIENE-CÁDIZ".

This paper describes the protocol for a study designed to address the high prevalence (40%) of childhood overweight and obesity in the province of Cádiz, Spain, as a reflection of what is happening worldwide. It is widely known that children who suffer from childhood obesity have a higher risk of developing chronic diseases in adulthood. This causes a decrease in the quality of life and an increase in health spending. In this context, it is necessary to intervene promoting healthy lifestyle habits from an early stage. The objective of this project will be to evaluate the effectiveness of a multimodal intervention (individual, school and family) called "PREVIENE-CÁDIZ" [CADIZ-PREVENT]. The intervention will be focused mainly on diet, physical activity, sedentary lifestyle and sleep, to prevent overweight and obesity in schoolchildren from 8 to 9 years old in the province of Cádiz. It will consist of a 10-session education program carried out in the classroom by the teachers. In addition, children will be assigned two workbooks, one to work on in class and the other at home with parents. A workshop aimed at parents will be included to help teach them how to obtain healthier lifestyle habits. The proposed study will involve a quasi-experimental design with a control group.

Development and Validation of a Safety Scale Perceived by the Witness of Prehospital Emergency Care.

OBJECTIVE: The aim of the study was to design and validate a new tool to measure the security perceived by witnesses of patient care and hospital transfers, after requesting urgent assistance via the "061" phone number. METHODS: This is a descriptive observational, cross-sectional, design, and validation study of a scale conducted by telephone interview. Witnesses of urgent assistance and transfers by prehospital emergency medical services in the province of Cadiz, in the south of Spain, were the subjects of study. A questionnaire was designed after focus groups with patients, witnesses, and professionals. It consisted of 10 items, with Likert-type answers, and a range of 0 to 50 points. In addition to basic criteria (frequency of endorsement and ability to discriminate between groups), their validity (content and construct) and reliability (stability and homogeneity) were evaluated. Stability was evaluated by test-retest and homogeneity by means of two properties: internal consistency of items (corrected item-scale correlation coefficient) and internal consistency of the scale (Cronbach α coefficient). RESULTS: A total of 849 questionnaires were obtained, with scores between 0 and 50 points, with an average of 47.31 (median of 50). The exploratory factor analysis detected a component that explained 61.1% of the total variance. The intraclass correlation coefficient was 0.933 with 95% confidence interval between 0.900 and 0.954. The corrected item-scale correlation coefficient was greater than 0.596, and the Cronbach α coefficient was 0.927 (95% confidence interval, 0.919-0.934). CONCLUSIONS: The ESPT10 Witness Perceived Safety Scale is valid and reliable for quantifying the safety perception of witnesses of emergency assistance and transfers.

¿Qué es el grupoanálisis? / What is group analysis?

En este trabajo exponemos las características de lo que para nosotros es el grupoanálisis, diferenciándolo de otras formas de psicoterapia de grupo. Es el resultado de nuestros años de experiencia y aprendizaje. Explicamos también los criterios formativos emanados de la European Group Analytic Training Institutions Network (EGATIN), que son los que se siguen en los cursos formativos de los que formamos parte. (AU)

In this paper we expose the characteristics of what group analysis is for us, differentiating it from other forms of group psychotherapy. This is derived from our clinical experience and training process. We also explain the training criteria decided by the European Group Analytic Training Institutions Network (EGATIN), which are the ones we follow in the training courses we lead. (AU)

Feeling safe or unsafe in prehospital emergency care: A qualitative study of the experiences of patients, carers and healthcare professionals.

AIMS AND OBJECTIVES: To determine the feelings of safety among patients taken to hospital after requesting urgent care, based on their experiences and those of their carers and prehospital emergency care professionals. BACKGROUND: Little research has been performed into the perception of safety in prehospital emergency care settings worldwide, from either the perspective of the patients or from that of healthcare professionals. DESIGN: Exploratory qualitative study using focus groups in Spain. METHODS: The participants were patients that requested care through the emergency telephone service, their carers and the professionals of the emergency care teams. The structured sampling design was based on an intentional, nonprobability selection following pragmatic criteria. Seven groups of patients/carers and two groups of professionals were formed (65 participants). The recordings were fully transcribed before their validation and codes were assigned to ensure anonymity. The ATLAS.ti software was used for the analysis. The authors took into account the COREQ checklist for qualitative studies. FINDINGS: Neither group provided a clear definition of the meaning of feeling safe. It appeared easier to give examples that had a positive or negative influence on their perception of feeling safe. During the analysis of the discourse, six categories were detected after grouping the related codes. CONCLUSIONS: For most of the patients' feeling of being safe or very safe arose from the perception of calmness, trust and protection. Defining the perception of safety was not easy. The factors with the greatest effect on feeling safe were related to Information and communication, Person-centred care and Professional competency, without losing sight of other factors such as Accessibility and response times of the emergency teams, Equipment and Healthcare setting. RELEVANCE TO CLINICAL PRACTICE: The findings could be used as a knowledge base in future research and for implementing procedures for improving perceptions of safety among patients.

Mesenchymal stromal cells for the prophylaxis and treatment of graft-versus-host disease-a meta-analysis.

BACKGROUND: Graft-versus-host disease (GvHD) is the main life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Thirty to 80% of GvHD patients do not respond to first-line treatment and a second-line treatment is not universally established. Based on their immunomodulatory properties, mesenchymal stromal cells (MSC) have been proposed for the prevention and the treatment of GvHD in patients undergoing HSCT. Unfortunately, previous studies reported conflicting results regarding the prophylactic and therapeutic effects of MSC for GvHD. Consequently, we carried out a meta-analysis to clarify whether MSC administration can improve the dismal outcome of these patients. METHODS: We carried out a systematic review and selected studies (2004-2019) reporting data about the administration of allogeneic MSC for the prevention (n = 654 patients) or treatment of acute (n = 943 patients) or chronic (n = 76 patients) GvHD after HSCT. Our primary outcome was overall survival at the last follow-up. The secondary outcomes were the response and development of GvHD. Subgroup analyses included age, MSC dose, first infusion day after HSCT, number of organs and organ-specific involvement, acute GvHD grade (I-IV), and chronic GvHD grade (limited or extensive). RESULTS: Patients infused with MSC for GvHD prophylaxis showed a 17% increased overall survival (95% CI, 1.02-1.33) and a reduced incidence of acute GvHD grade IV (RR = 0.22; 95% CI, 0.06-0.81) and chronic GvHD (RR = 0.64; 95% CI, 0.47-0.88) compared with controls. Overall survival of acute GvHD patients (0.50; 95% CI, 0.41-0.59) was positively correlated with MSC dose (P = 0.0214). The overall response was achieved in 67% (95% CI, 0.61-0.74) and was complete in 39% (95% CI, 0.31-0.48) of acute patients. Organ-specific response was higher for the skin. Twenty-two percent (95% CI, 0.16-0.29) of acute patients infused with MSC developed chronic GvHD. Sixty-four percent (95% CI, 0.47-0.80) of chronic patients infused with MSC survived; the overall response was 66% (95% CI, 0.55-0.76) and was complete in 23% (95% CI 0.12-0.34) of patients. CONCLUSIONS: Our meta-analysis indicates that allogeneic MSC could be instrumental for the prophylaxis and treatment of GvHD. Future trials should investigate the effect of the administration of MSC as an adjuvant therapy for the treatment of patients with GvHD from the onset of the disease.

Detección y evaluación del papel de la sarcopenia en ancianos con cáncer tratados con quimioterapia. Proyecto ONCOSARCO / Detection and evaluation of the role of sarcopenia in elderly patients with cancer treated with chemotherapy. ONCOSARCO project

Objetivos. Objetivos principales: elaborar un modelo predictor de toxicidad a la quimioterapia en ancianos oncológicos, a partir de variables relacionadas con la sarcopenia; identificar cuál de estos parámetros, sarcopenia o fragilidad, es el mejor predictor de toxicidad de la quimioterapia en ancianos. Material y métodos. Estudio prospectivo observacional, con pacientes ≥70 años tratados con quimioterapia en la Unidad de Cáncer en el Anciano de la Sección de Oncología Médica del Hospital Virgen de la Luz de Cuenca. Antes del inicio de la quimioterapia, a cada paciente se le determinará la fuerza muscular (handgrip, fuerza cilíndrica manual, fuerza de presión pulgar, flexión de cadera, extensión de rodilla), la masa muscular (índice de masa muscular esquelética) y la función física (velocidad 5 metros y test 5-Sit to stand). A lo largo de los 4 meses de tratamiento con quimioterapia, se recogerá la aparición de toxicidad severa. Se evaluará, mediante un primer análisis de regresión logística multinomial, cuál de ellos, sarcopenia (definición del European Working Group on Sarcopenia in Older People o fragilidad (criterios propuestos por Fried et al.), es el mejor predictor de toxicidad de la quimioterapia. Mediante un segundo análisis de regresión se pretende crear el primer modelo de predicción de toxicidad a la quimioterapia en el anciano oncológico, basado en la definición de sarcopenia. Conclusiones. Se espera que del análisis definitivo de este proyecto puedan encontrarse factores predictores de toxicidad a quimioterapia en ancianos oncológicos (AU)

Objectives. To develop a predictive model of toxicity to chemotherapy in elderly patients with cancer, using the variables associated with sarcopenia, and to identify which of these parameters, sarcopenia or frailty, is the best predictor of toxicity to chemotherapy in the elderly. Material and methods. A prospective observational study with patients ≥70 years treated with chemotherapy in the Cancer Unit for the Elderly, in the Medical Oncology Section of the Hospital Virgen de la Luz de Cuenca. The following tests will be performed by each patient before chemotherapy: muscle strength (handgrip, cylindrical handgrip, pinch gauge, hip flexion, knee extension), muscle mass (skeletal muscle mass index), and physical function (gait speed and 5STS test). The occurrence of severe toxicity will be recorded over a period of 4 months of chemotherapy treatment. It will be evaluated, using logistic regression analysis, whether sarcopenia (defined by the European Working Group on Sarcopenia in Older People) or frailty (defined by the phenotype of frailty) is the best predictor of chemotherapy toxicity. Using a multinomial logistic regression analysis, we will try to create the first model to predict toxicity to chemotherapy in elderly patients with diagnosis of cancer, based on the definition of sarcopenia. Conclusions. It is expected that the final analysis of this project will be useful to detect predictive factors of toxicity to chemotherapy in elderly patients with cancer (AU)

[Detection and evaluation of the role of sarcopenia in elderly patients with cancer treated with chemotherapy. ONCOSARCO project]. / Detección y evaluación del papel de la sarcopenia en ancianos con cáncer tratados con quimioterapia. Proyecto ONCOSARCO.

OBJECTIVES: To develop a predictive model of toxicity to chemotherapy in elderly patients with cancer, using the variables associated with sarcopenia, and to identify which of these parameters, sarcopenia or frailty, is the best predictor of toxicity to chemotherapy in the elderly. MATERIAL AND METHODS: A prospective observational study with patients ≥70 years treated with chemotherapy in the Cancer Unit for the Elderly, in the Medical Oncology Section of the Hospital Virgen de la Luz de Cuenca. The following tests will be performed by each patient before chemotherapy: muscle strength (handgrip, cylindrical handgrip, pinch gauge, hip flexion, knee extension), muscle mass (skeletal muscle mass index), and physical function (gait speed and 5STS test). The occurrence of severe toxicity will be recorded over a period of 4 months of chemotherapy treatment. It will be evaluated, using logistic regression analysis, whether sarcopenia (defined by the European Working Group on Sarcopenia in Older People) or frailty (defined by the phenotype of frailty) is the best predictor of chemotherapy toxicity. Using a multinomial logistic regression analysis, we will try to create the first model to predict toxicity to chemotherapy in elderly patients with diagnosis of cancer, based on the definition of sarcopenia. CONCLUSIONS: It is expected that the final analysis of this project will be useful to detect predictive factors of toxicity to chemotherapy in elderly patients with cancer.

Prognostic Role of Early and End-of-Neoadjuvant Treatment 18F-FDG PET/CT in Patients With Breast Cancer.

AIM: To determine the use of early and final treatment F-FDG PET/CT in the prediction of response to neoadjuvant chemotherapy (NAC) and its role in the prognosis of patients with locally advanced breast cancer (LABC). METHODS: One hundred thirty-two patients underwent a baseline FDG PET/CT (PET-1) after the second course of chemotherapy (PET-2) and after the last course (PET-3). Breast tumors were categorized into molecular phenotypes and risk categories according to the biological prognostic factors obtained by immunohistochemistry. PET/CT scans were semiquantitatively evaluated, obtaining the Δ% SUV1-2 and SUV1-3 in primary tumor and axillary lymph nodes to establish response groups attending to EORTC criteria. Moreover, a binary assessment was obtained classifying the studies as positive or negative. Histopathological response was obtained in breast and lymph node specimens. Overall survival (OS) and disease-free survival (DFS) were obtained after the follow-up. ROC analysis was performed to determine a cutoff value of Δ% SUV1-2 and SUV1-3 for the prediction of response and prognosis. Relations between phenotypes, metabolic behavior, final histopathological response, OS, and DFS were evaluated. RESULTS: In binary analysis, only PET-3 was able to predict histopathological response in lymph nodes. The cutoff values of %Δ SUV1-2 and %Δ SUV1-3 with the best sensitivity and specificity in the prediction of response in breast tumor were 62% (Se: 70% and Sp: 69%) and 84% (Se: 70% and Sp: 88%). A %ΔSUV1-3 of 74% in breast tumor was a predictor of DFS (AUC = 0.647; P = 0.037, Se: 52% and Sp: 66%). Kaplan-Meier analysis revealed significant relations between the binary lymph node assessment of PET-3 with OS (P = 0.016, χ = 5.78) and DFS (P = 0.003, χ = 9.10). CONCLUSIONS: End-of-treatment F-FDG PET/CT was a predictor of lymph node response and prognosis. Most of metabolic response variables related to histopathological response showed association with the prognosis.