Cross-sectional and longitudinal associations of adherence to WCRF/AICR cancer prevention recommendations with health-related quality of life in breast cancer survivors. Health-EpiGEICAM study.

OBJECTIVES: Adherence to healthy lifestyle recommendations has been reported to improve health-related quality of life (HRQL) in breast cancer (BC) patients, but the influence of long-term behavioral changes remains unknown. We evaluated the association between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and HRQL both, at BC diagnosis and the change 7-12 years later. DESIGN: Prospective cohort study. SETTINGS AND PARTICIPANTS: A total of 406 breast cancer survivors, from the EpiGEICAM study, were recruited in 16 Spanish hospitals. MEASUREMENTS: Epidemiological, clinical, dietary, physical activity and HRQL information was collected both at recruitment and 7-12 years later. A 7-item score to measure compliance with recommendations was assessed according to the 2018 WCRF/AICR scoring criteria. HRQL was evaluated using SF-36 questionnaire. Linear mixed models for longitudinal data were used to assess the cross-sectional and longitudinal association between adherence score and the physical and mental component summary scores. RESULTS: At diagnosis, for each unit increase in WCRF/AICR score adherence, the HRQL physical domain increased 0.78 points (95%CI: -0.04 to 1.60; P trend:0.06). The mean change in physical HRQL from diagnosis to follow-up per unit increase in within-subject adherence score was 0.73 points (95%CI: -0.18 to 1.65; P trend: 0.12). For the mental domain, no association was observed with compliance with the recommendations at diagnosis, nor with changes in adherence over time. CONCLUSIONS: Our results suggest that Increased adherence to WCRF/AICR cancer prevention recommendations over time could contribute to slightly improved long-term physical HRQoL in BC survivors.

Comparative biological activity of palbociclib and ribociclib in hormone receptor-positive breast cancer.

This study examines the biological effects of palbociclib and ribociclib in hormone receptor-positive breast cancer, pivotal to the HARMONIA prospective phase III clinical trial. We explore the downstream impacts of these CDK4/6 inhibitors, focusing on cell lines and patient-derived tumor samples. We treated HR+ breast cancer cell lines (T47D, MCF7, and BT474) with palbociclib or ribociclib (100 nM or 500 nM), alone or combined with fulvestrant (1 nM), over periods of 24, 72, or 144 h. Our assessments included PAM50 gene expression, RB1 phosphorylation, Lamin-B1 protein levels, and senescence-associated ß-galactosidase activity. We further analyzed PAM50 gene signatures from the CORALLEEN and NeoPalAna phase II trials. Both CDK4/6 inhibitors similarly inhibited proliferation across the cell lines. At 100 nM, both drugs partially reduced p-RB1, with further decreases at 500 nM over 144 h. Treatment led to reduced Lamin-B1 expression and increased senescence-associated ß-galactosidase activity. Both drugs enhanced Luminal A and reduced Luminal B and proliferation signatures at both doses. However, the HER2-enriched signature significantly diminished only at the higher dose of 500 nM. Corresponding changes were observed in tumor samples from the CORALLEEN and NeoPalAna studies. At 2 weeks of treatment, both drugs significantly reduced the HER2-enriched signature, but at surgery, this reduction was consistent only with ribociclib. Our findings suggest that while both CDK4/6 inhibitors effectively modulate key biological pathways in HR+/HER2- breast cancer, nuances in their impact, particularly on the HER2-enriched signature, are dose-dependent, influenced by the addition of fulvestrant and warrant further investigation.

Cell-cycle inhibition and immune microenvironment in breast cancer treated with ribociclib and letrozole or chemotherapy.

In this study, we performed genomic analyses of cell cycle and tumor microenvironment changes during and after ribociclib and letrozole or chemotherapy in the CORALLEEN trial. 106 women with untreated PAM50-defined Luminal B early breast cancers were randomly assigned to receive neoadjuvant ribociclib and letrozole or standard-of-care chemotherapy. Ki67 immunohistochemistry, tumor-infiltrating lymphocytes quantification, and RNA sequencing were obtained from tissue biopsies pre-treatment, on day 14 of treatment, and tumor specimens from surgical resection. Results showed that at surgery, Ki67 and the PAM50 proliferation scores were lower after ribociclib compared to chemotherapy. However, consistent reactivation of tumor cell proliferation from day 14 to surgery was only observed in the ribociclib arm. In tumors with complete cell cycle arrest (CCCA) at surgery, PAM50 proliferation scores were lower in the ribociclib arm compared to chemotherapy (p < 0.001), whereas the opposite was observed with tumor cellularity (p = 0.002). Gene expression signatures (GES) associated with antigen-presenting cells (APCs) and innate immune system activity showed increased expression post-chemotherapy but decreased expression post-ribociclib. Interferon-associated GES had decreased expression with CCCA and increased expression with non-CCCA. Our findings suggest that while both treatment strategies decreased proliferation, the depth and the patterns over time differed by treatment arm. Immunologically, ribociclib was associated with downregulated GES associated with APCs and the innate immune system in Luminal B tumors, contrary to existing preclinical data. Further studies are needed to understand the effect of CDK4/6 inhibition on the tumor cells and microenvironment, an effect which may vary according to tumor subtypes.

Single-agent metronomic versus weekly oral vinorelbine as first-line chemotherapy in patients with HR-positive/HER2-negative advanced breast cancer: The randomized Tempo Breast study.

INTRODUCTION: Single-agent oral vinorelbine is a standard of care for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that has progressed on endocrine therapy. Metronomic administration may offer a better balance of efficacy and safety than standard regimens, but data from previous trials are scarce. METHODS: In this open-label, multicenter, phase II trial, patients were randomized to oral vinorelbine administered on a metronomic (50 mg three times weekly) or weekly (60 mg/m2 in cycle 1, increasing to 80 mg/m2 if well tolerated) schedule. Treatment was continued until disease progression or intolerance. The primary endpoint was disease control rate (DCR, the proportion of patients with a best overall confirmed response of CR, PR, or stable disease lasting 6 months or more). RESULTS: One-hundred sixty-three patients were randomized and treated. The DCR was 63.4% (95% confidence interval [CI]: 52.0-73.8) with metronomic vinorelbine and 72.8% (95% CI: 61.8-82.1) with weekly vinorelbine. Weekly vinorelbine was also associated with longer progression-free survival (5.6 vs 4.0 months) and overall survival (26.7 vs 22.3 months) than metronomic vinorelbine, but was associated with more adverse events. CONCLUSIONS: In this randomized phase II trial, single-agent metronomic oral vinorelbine was effective and well tolerated as first-line chemotherapy for patients with HR-positive/HER2-negative ABC. Formal comparisons are not done in this phase II study and one can simply observe that confidence intervals of all endpoints overlap. When deciding for a chemotherapy after failure of endocrine therapy and CDK 4/6 inhibitors, oral vinorelbine might be an option to be given with either schedule. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2014-003860-19.

[Efficacy of Physiotherapy Interventions on the Respiratory Musculature Through Respiratory Training Techniques in Post-operative Lung Transplant Recipients: Systematic Review]. / Eficacia de las intervenciones fisioterápicas sobre la musculatura respiratoria mediante técnicas de entrenamiento respiratorio en el postoperatorio de trasplantados pulmonares: una revisión sistemática.

Introduction: Respiratory muscles are a limiter of exercise capacity in lung transplant patients. It is necessary to know the effectiveness of specific respiratory muscle training techniques carried out in the management of adult lung transplant patients in the postoperative period. Methodology: A systematic review of clinical trials was carried out, which included adult lung transplant patients undergoing post-transplant respiratory training. A search was carried out in the databases PubMed/Medline, EMBASE, Scopus, Web of Science, Cochrane Library between January 2012 and September 2023, using the terms: "breathing exercise", "respiratory muscle training", "inspiratory muscle training", "respiratory exercise", "pulmonary rehabilitation", "lung rehabilitation"; in combination with "lung transplantation", "lung transplant", "posttransplant lung". No language limit. Results: Eleven trials were included with a total of 639 patients analyzed. Most training programs begin upon hospital discharge (more than one month post-transplant), few do so early (Intensive Care Unit). The duration varies from 1-12 months post-transplant. The interventions were based on aerobic training and peripheral muscle strength. Some of them included breathing exercises and chest expansions. The most used outcome variable was submaximal exercise capacity measured with the 6-minute walk test. Conclusions: Training the respiratory muscles of the adult transplant patient favors the improvement of exercise capacity and quality of life. Aerobic training, as well as strength training of the rest of the peripheral muscles, contribute to the improvement of respiratory muscles.

Resultados obstétricos y neonatales relacionados con la hidratación intraparto en mujeres atendidas de parto de bajo riesgo / Obstetric and neonatal results associated with intrapartum hydration for women with low-risk labour

Objetivo: determinar la influencia de la hidratación intraparto en los resultados obstétricos y neonatales en mujeres nulíparas atendidas por parto de bajo riesgo.Métodos: se realizó un estudio observacional prospectivo en el Hospital Universitario Puerta de Hierro Majadahonda (Madrid, España). Se incluyeron mujeres nulíparas con gestación única atendidas por parto de bajo riesgo. Se recogieron variables maternas (sociodemográficas, clínicas al ingreso, intraparto y en el puerperio inmediato, resultados obstétricos) y neonatales (datos al nacimiento, a las 24 y 48 horas). Se realizó análisis descriptivo y univariante con los test estadísticos correspondientes. Se valoró la influencia de la hidratación en los resultados obstétricos y neonatales estableciendo un punto de corte en la hidratación recibida intraparto (mediana volumen total administrado por hora: 300 mL/h).Resultados: se incluyeron 148 mujeres. Edad media (DE) 32 (4,4) años, edad gestacional media (DE) 39 (1,4) semanas. Al ingreso, la dilatación media fue de 2 cm. Parto inducido en 65,5% (n= 97). Los resultados obstétricos y neonatales fueron más favorables en las mujeres que recibieron un volumen mayor(> 300 mL/h), con diferencias significativas en la duración total del parto (mediana 526 vs. 735 min; p< 0,001), incidencia de parto por cesárea (14,3% frente 18,7%), fiebre (5,5% frente a 7,7%), incidencia de pérdida de peso neonatal superior al 7% a las 48 horas (28,6% frente a 39,8%), lactancia materna (94,6% frente a 82,4%).Conclusiones: la administración de un mayor volumen de líquidos a mujeres nulíparas durante el parto de bajo riesgo se asoció con mejores resultados obstétricos y neonatales.(AU)

Objective: to determine the influence of intrapartum hydration on obstetric and neonatal results in nulliparous women during low-risk labour.Methods: an observational prospective study was conducted at the Hospital Universitario Puerta de Hierro Majadahonda (Madrid, Spain). The study included nulliparous women with single pregnancy and low-risk labour. Maternal variables were collected (sociodemographic, clinical signs at admission, intrapartum and immediately post-partum, obstetric results) as well as neonatal variables (data at birth, at 24 and 48 hours). Descriptive and univariate analysis was conducted with the relevant statistic tests. The influence of hydration was assessed in obstetric and neonatal results, determining a cut-off point for the hydration received intrapartum (median total volume administered per hour: 300 mL/h).Results: the study included 148 women, with a mean age (SD) of 32 (4.4) years, and a mean gestational age (SD) of 39 (1.4) weeks. At admission, mean dilation was of 2 cm. There was induced labour in 65.5% of cases (n= 97). Obstetric and neonatal results were more favourable in those women who received a higher volume (≥ 300 mL/h), with significant differences in the total duration of labour (median 526 vs. 735 min; p< 0.001), incidence of Caesarean births (14.3% vs. 18.7%), fever (5.5% vs. 7.7%), incidence of neonatal weight loss >7% at 48 hours (28.6% vs. 39.8%), breastfeeding (94.6% vs. 82.4%).Conclusions: administration of a higher volume of fluids to nulliparous women during low-risk labour was associated with better obstetric and neonatal results.(AU)

Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Álamo IV registry.

PURPOSE: The monarchE trial showed that the addition of abemaciclib improves efficacy in patients with high-risk early breast cancer (EBC). We analyzed the long-term outcomes of a population similar to the monarchE trial to put into context the potential benefit of abemaciclib. METHODS: HR-positive/HER2-negative EBC patients eligible for the monarchE study were selected from 3 adjuvant clinical trials and a breast cancer registry. Patients with ≥ 4 positive axillary lymph nodes (N +) or 1-3 N + with tumor size ≥ 5 cm and/or histologic grade 3 and/or Ki67 ≥ 20%, who had undergone surgery with curative intent and had received anthracyclines ± taxanes and endocrine therapy in the neoadjuvant and /or adjuvant setting were included. We performed analysis of Invasive Disease-Free Survival (iDFS), Distant Disease-Free Survival (dDFS) and Overall Survival (OS) at 5 and 10 years, as well as yearly (up to 10) of Invasive Relapse Rate (IRR), Distant Relapse Rate (DRR) and Death Rate (DR). RESULTS: A total of 1,617 patients were analyzed from the GEICAM-9906 (312), GEICAM-2003-10 (210), and GEICAM-2006-10 (160) trials plus 935 from El Álamo IV. With a median follow-up of 10.1 years, the 5 and 10 years iDFS rates were 75.2% and 57.0%, respectively. The dDFS and OS rates at 5 years were 77.4% and 88.8% and the respective figures at 10 years were 59.7% and 70.9%. CONCLUSIONS: This data points out the need for new therapies for those patients. A longer follow-up of the monarchE study to see the real final benefit with abemaciclib is warranted. TRIAL REGISTRATION: ClinTrials.gov: GEICAM/9906: NCT00129922; GEICAM/ 2003-10: NCT00129935 and GEICAM/ 2006-10: NCT00543127.

Analysis of Local Recurrence Risk in Ductal Carcinoma In Situ and External Validation of the Memorial Sloan Kettering Cancer Center Nomogram.

BACKGROUND: Adjuvant radiotherapy and hormonotherapy after breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) have been shown to reduce the risk of local recurrence. To predict the risk of ipsilateral breast tumor relapse (IBTR) after BCS, the Memorial Sloan Kettering Cancer Center (MSKCC) developed a nomogram to analyze local recurrence (LR) risk in our cohort and to assess its external validation. METHODS: A historical cohort study using data from 296 patients treated for DCIS at the Hospital Clínic of Barcelona was carried out. Patients who had had a mastectomy were excluded from the analysis. RESULTS: The mean age was 58 years (42-75), and the median follow-up time was 10.64 years. The overall local relapse rate was 13.04% (27 patients) during the study period. Actuarial 5- and 10-year IBTR rates were 5.8 and 12.9%, respectively. The external validation of the MSKCC nomogram was performed using a multivariate logistic regression analysis on a total of 207 patients, which did not reach statistical significance in the studied population for predicting LR (p = 0.10). The expression of estrogen receptors was significantly associated with a decreased risk of LR (OR: 0.25; p = 0.004). CONCLUSIONS: In our series, the LR rate was 13.4%, which was in accordance with the published series. The MSKCC nomogram did not accurately predict the IBTR in this Spanish cohort of patients treated for DCIS (p = 0.10).

HOPE (SOLTI-1903) breast cancer study: real-world, patient-centric, clinical practice study to assess the impact of genomic data on next treatment decision-choice in patients with locally advanced or metastatic breast cancer.

Background: Metastatic breast cancer (mBC) causes nearly all BC-related deaths. Next-generation sequencing (NGS) technologies allow for the application of personalized medicine using targeted therapies that could improve patients' outcomes. However, NGS is not routinely used in the clinical practice and its cost induces access-inequity among patients. We hypothesized that promoting active patient participation in the management of their disease offering access to NGS testing and to the subsequent medical interpretation and recommendations provided by a multidisciplinary molecular advisory board (MAB) could contribute to progressively overcome this challenge. We designed HOPE (SOLTI-1903) breast cancer trial, a study where patients voluntarily lead their inclusion through a digital tool (DT). The main objectives of HOPE study are to empower mBC patients, gather real-world data on the use of molecular information in the management of mBC and to generate evidence to assess the clinical utility for healthcare systems. Trial design: After self-registration through the DT, the study team validates eligibility criteria and assists patients with mBC in the subsequent steps. Patients get access to the information sheet and sign the informed consent form through an advanced digital signature. Afterwards, they provide the most recent (preferably) metastatic archival tumor sample for DNA-sequencing and a blood sample obtained at the time of disease progression for ctDNA analysis. Paired results are reviewed by the MAB, considering patient's medical history. The MAB provides a further interpretation of molecular results and potential treatment recommendations, including ongoing clinical trials and further (germline) genetic testing. Participants self-document their treatment and disease evolution for the next 2 years. Patients are encouraged to involve their physicians in the study. HOPE also includes a patient empowerment program with educational workshops and videos about mBC and precision medicine in oncology. The primary endpoint of the study was to describe the feasibility of a patient-centric precision oncology program in mBC patients when a comprehensive genomic profile is available to decide on a subsequent line of treatment. Clinical trial registration: www.soltihope.com, identifier NCT04497285.

Características clínicas y laborales de los trabajadores de un hospital universitario con signos y síntomas de COVID-19 durante la pandemia / Clinical and occupational characteristics of university hospital workers with COVID-19 signs and symptoms during the pandemic

Objetivo: conocer las características sociodemográficas, laborales y la exposición al riesgo en trabajadores de un hospital universitario que presentaron síntomas COVID-19 durante la primera ola de la pandemia. Métodos: estudio transversal (julio-septiembre 2020) a personal del Hospital Puerta de Hierro Majadahonda (Madrid, España) que trabajó en la primera ola de la pandemia. Se diseñó una encuesta ad hoc, que incluía: perfil del trabajador, síntomas COVID-19, exposición, curso clínico y atención sanitaria, entre otros. Se realizó un análisis descriptivo. Se usó Chi cuadrado y t de Student para el contraste de hipótesis. Resultados: 992 sujetos. El 34,3% (n= 340) presentó síntomas COVID-19. 283 (84,0%) eran mujeres. El 82,9% (n= 282), personal sanitario. El 36,8% (n= 125), enfermeras. El 63,5% (n= 216) trabajó en unidades de alto riesgo. El 36,2% (n= 123) tenía patología previa. El 83,3% (n= 194) reconoció haber trabajado previamente en unidades de alto riesgo. El 84,5% (n= 229) manifestó haberse sentido expuesto a la infección durante el trabajo. El 49,7% (n= 98) tuvo alguna incidencia de riesgo. El 73,7% (n= 202) presentó astenia. Hubo mayor prevalencia de personal sanitario con síntomas COVID-19 frente a no sanitario en función del trabajo asistencial (92,9% frente a 50,0%; p< 0,001), área de trabajo COVID-19 (74,2% frente a 48,1%; p< 0,001), actividad en Unidades de riesgo alto (73,4% frente a 15,5%; p< 0,001). Conclusiones: entre trabajadores con síntomas COVID hubo una mayor proporción de personal sanitario, mujeres, enfermeras, trabajadores en áreas COVID-19, unidades de riesgo, con exposición previa con pacientes infectados/sospecha. Las diferencias entre trabajadores sanitarios y no sanitarios vienen determinadas por el lugar de trabajo durante la pandemia y el riesgo de exposición a la COVID-19.(AU)

Objective: to understand the sociodemographic and occupational characteristics and risk exposure among workers of a university hospital who presented COVID-19 symptoms during the first wave of the pandemic. Methods: a cross-sectional study (July to September 2020), on staff from the Hospital Puerta de Hierro Majadahonda (Madrid, Spain) who were working during the first wave of the pandemic. An ad hoc survey was designed, which included the worker profile, COVID-19 symptoms, exposure, clinical course, and healthcare, among others. Descriptive analysis was conducted, and Chi-square and Student’s t-test were used for statistical hypothesis testing. Results: the study included 992 subjects; 34.3% (n= 340) presented COVID-19 symptoms; 283 (84.0%) were female; 82.9% (n= 282) of them were healthcare staff; 36.8% (n= 125) were nurses; 63.5% (n= 216) worked at high risk units; 36.2% (n= 123) had a previous medical condition. Of the participants, 83.3% (n= 194) admitted having worked previously at high risk units; 84.5% (n= 229) stated that they have felt exposed to the infection during work; 49.7% (n= 98) had some incidence of risk; and 73.7% (n= 202) presented asthenia. There was a higher prevalence of healthcare staff with COVID symptoms vs. non-healthcare staff, based on care activities (92.9% vs. 50.0%; p< 0.001), work at COVID areas (74.2% vs. 48.1%; p< 0.001), and activity in high risk Units (73.4% vs. 15.5%; p< 0.001). Conclusions: among the workers with COVID symptoms, there was a higher proportion of healthcare staff, women, nurses, workers at COVID areas, risk units, and previous exposure to patients with confirmed or suspected infection. Differences between healthcare and non-healthcare staff were determined by their place of work during the pandemic and their risk of exposure to COVID-19.(AU)

Circulating tumor DNA reveals complex biological features with clinical relevance in metastatic breast cancer.

Liquid biopsy has proven valuable in identifying individual genetic alterations; however, the ability of plasma ctDNA to capture complex tumor phenotypes with clinical value is unknown. To address this question, we have performed 0.5X shallow whole-genome sequencing in plasma from 459 patients with metastatic breast cancer, including 245 patients treated with endocrine therapy and a CDK4/6 inhibitor (ET + CDK4/6i) from 2 independent cohorts. We demonstrate that machine learning multi-gene signatures, obtained from ctDNA, identify complex biological features, including measures of tumor proliferation and estrogen receptor signaling, similar to what is accomplished using direct tumor tissue DNA or RNA profiling. More importantly, 4 DNA-based subtypes, and a ctDNA-based genomic signature tracking retinoblastoma loss-of-heterozygosity, are significantly associated with poor response and survival outcome following ET + CDK4/6i, independently of plasma tumor fraction. Our approach opens opportunities for the discovery of additional multi-feature genomic predictors coming from ctDNA in breast cancer and other cancer-types.

mHealth Technology as a Help Tool during Breast Cancer Treatment: A Content Focus Group.

PURPOSE: To assess the usability and preferences of the contents of mHealth software developed for breast cancer patients as a tool to obtain patient-reported outcomes (PROMs), improve the patient's knowledge about the disease and its side effects, increase adherence to treatment, and facilitate communication with the doctor. INTERVENTION: an mHealth tool called the Xemio app provides side effect tracking, social calendars, and a personalized and trusted disease information platform to deliver evidence-based advice and education for breast cancer patients. METHOD: A qualitative research study using semi-structured focus groups was conducted and evaluated. This involved a group interview and a cognitive walking test using Android devices, with the participation of breast cancer survivors. RESULTS: The ability to track side effects and the availability of reliable content were the main benefits of using the application. The ease of use and the method of interaction were the primary concerns; however, all participants agreed that the application would be beneficial to users. Finally, participants expressed their expectations of being informed by their healthcare providers about the launch of the Xemio app. CONCLUSION: Participants perceived the need for reliable health information and its benefits through an mHealth app. Therefore, applications for breast cancer patients must be designed with accessibility as a key consideration.

Factores asociados con los signos y síntomas de COVID-19 en los profesionales sanitarios de un hospital universitario español durante la pandemia / Factors associated with covid-19 signs and symptoms in healthcare professionals at a spanish university hospital during the pandemic

Objetivos: El objetivo del estudio fue identificar los factores asociados al desarrollo de COVID-19 en profesionales sanitarios de un hospital universitario al inicio de la pandemia. Material y Métodos: Estudio transversal mediante encuesta online validada en aspecto y contenido, pre-test cognitivo y pilotaje dirigida a los profesionales sanitarios. Se describieron las frecuencias absolutas y relativas para variables cualitativas y cuantitativas, se analizaron las asociaciones mediante la prueba chi-cuadrado para cualitativas y t de Student para cuantitativas. Se realizó una regresión logística para identificar los factores asociados a la COVID-19 en profesionales sanitarios. Resultados: Participaron 728 sujetos. Se observaron diferencias estadísticamente significativas en el tipo de trabajo (p=0,041), exposición relacionada con los espacios y la organización (p=0,001), patología previa (p=0,029) y asma (p=0,034). Los profesionales sanitarios que trabajaron en áreas asistenciales del hospital presentaron la mayor probabilidad de desarrollar COVID-19 (OR: 2,02; p=0,027) y también en aquellos con exposición relacionada con los espacios y organización (OR: 2,13; p≤0,001). Conclusión: Los profesionales sanitarios que trabajaron en áreas asistenciales del hospital presentaron el doble de probabilidad de desarrollar COVID-19. Lo mismo se observó para aquellos con exposición relacionada con los espacios. (AU)

Objectives: The aim of the study was to identify factors associated with the development of COVID-19 in healthcare professionals at a university hospital at the onset of the pandemic. Material and Methods: Cross-sectional study using an online survey validated in aspect and content, cognitive pre-test and piloting aimed at healthcare professionals. Absolute and relative frequencies were described for qualitative and quantitative variables, associations were analyzed using the chi-square test for qualitative variables and Student's t-test for quantitative variables. Logistic regression was performed to identify factors associated with COVID-19 in healthcare professionals. Results: 728 workers participated in the survey. Statistically significant differences were observed in type of work (p=0.041), exposure related to spaces and organisation (p=0.001), previous pathology (p=0.029) and asthma (p=0.034). Healthcare professionals working in care areas of the hospital were most likely to develop COVID-19 (OR: 2.02; p=0.027) and also in those with exposure related to space and organisation (OR: 2.13; p≤0.001). Conclusion: Healthcare professionals who worked in care areas of the hospital were twice as likely to develop COVID-19. The same was observed for those with space-related exposure. (AU)

Pain Behaviors Analyzed by Videorecording in Brain-Injured Patients Admitted to the Intensive Care Unit.

AIM: To describe and classify pain behaviors (facial and body) in brain-injured patients with a low level of consciousness before, during, and after the performance of painful and non-painful care procedures. METHODS: Facial behaviors and body movements in brain-injured patients were videotaped at rest, during the application of three care procedures (two painful and one non-painful), and 15 minutes after completion of these procedures. Each video recording was evaluated by expert evaluators blinded to each other. For each of the behaviors observed, all possible combinations between the three procedures and/or time were compared using the McNemar test. Effect size was measured by the difference in proportions using the Wilson score 95% confidence intervals. RESULTS: Twenty-seven patients were included. The mean (standard deviation) Glasgow Coma Score was 5.4 (1.9). A total of 33 behaviors (29 active, four neutral) were registered. Expression of behaviors was more common during the painful procedures compared with the other time points (non-painful procedures, baseline, and final evaluation). Inter-evaluator agreement was substantial (Kappa index >0.7) in more than 50% of the observed behaviors. CONCLUSIONS: In this study involving brain-injured patients with a low level of consciousness, facial, body, and ventilation-related behaviors were more common during painful procedures. Agreement between evaluators to detect the presence or absence of these behaviors was substantial. These findings underscore the need to develop pain assessment measures specific to this patient population.

HER2DX ERBB2 mRNA expression in advanced HER2-positive breast cancer treated with T-DM1.

In advanced HER2-positive (HER2+) breast cancer, the new antibody-drug conjugate trastuzumab deruxtecan is more effective compared with trastuzumab emtansine (T-DM1). However, trastuzumab deruxtecan can have considerable toxicities, and the right treatment sequence is unknown. Biomarkers to guide the use of anti-HER2 therapies beyond HER2 status are needed. Here, we evaluated if preestablished levels of ERBB2 mRNA expression according to the HER2DX standardized assay are associated with response and survival following T-DM1. In ERBB2 low, medium, and high groups, the overall response rate was 0%, 29%, and 56%, respectively (P < .001). ERBB2 mRNA was statistically significantly associated with better progression-free survival (P = .002) and overall survival (OS; P = .02). These findings were independent of HER2 immunohistochemistry (IHC) levels, hormone receptor, age, brain metastasis, and line of therapy. The HER2DX risk score (P = .04) and immunoglobulin signature (P = .04) were statistically significantly associated with overall survival since diagnosis. HER2DX provides prognostic and predictive information following T-DM1 in advanced HER2+ breast cancer.

Neoadjuvant endocrine therapy for luminal breast tumors: State of the art, challenges and future perspectives.

Neoadjuvant endocrine treatment (NET) associates to satisfactory rates of breast conservative surgery and conversions from inoperable to operable hormone receptor-positive (HR+)/HER2-negative breast cancer (BC), with less toxicities than neoadjuvant chemotherapy (NACT) and similar outcomes. Hence, it has been proposed as a logical alternative to NACT in patients with HR+/HER2- BC candidate to a neoadjuvant approach. Nevertheless, potential barriers to the widespread use of NET include the heterogeneous nature of patient response coupled with the long duration needed to achieve a clinical response. However, interest in NET has significantly increased in the last decade, owing to more in-depth investigation of several biomarkers for a more adequate patient selection and on-treatment benefit monitoring, such as PEPI score, Ki67 and genomic assays. This review is intended to describe the state-of-the-art regarding NET, its future perspectives and potential integration with molecular biomarkers for the optimal selection of patients, regimen and duration of (neo)adjuvant treatments.

Evaluación de las estrategias formativas digitales para profesionales sanitarios implementadas durante la pandemia por COVID-19 / Evaluation of the digital educational strategies for healthcare professionals implemented during the COVID-19 pandemic

Objetivo: evaluar la implementación de la estrategia educativa de microaprendizaje mediante el uso de una aplicación móvil para los profesionales sanitarios de un hospital universitario durante la pandemia por COVID-19. Método: se realizó una encuesta a trabajadores del hospital. Se monitorizaron las visualizaciones de las píldoras formativas. El cuestionario permitió recoger información del perfil sociodemográfico de los participantes, el uso de aplicaciones móviles formativas y el de las píldoras creadas ad hoc durante la pandemia por COVID-19. El número de usuarios registrados en la aplicación era de 4.572. Los datos obtenidos se analizaron mediante un análisis descriptivo, utilizándose la prueba T de Student y el test ANOVA para análisis bivariantes. Resultados: participaron 633 profesionales, edad media (DE) 44,8 (11,1) años. El 81,7% (n= 517) era mujer. El 93,5% (n= 592) era trabajador sanitario. Las enfermeras representaron el 41,2% (n= 261) y los médicos el 22,3% (n= 141). Durante la pandemia, el 55,8% (n= 353) de los sujetos del estudio había trabajado dando asistencia directa a pacientes COVID (+). El 94% (n= 595) utilizó la visualización de vídeos para formarse/informarse para su ámbito profesional. El 94,9% refirió conocer las píldoras formativas de la app Formación SanidadMadrid. Las 22 píldoras formativas recibieron 25.539 visualizaciones en total. Se registró alta satisfacción de los participantes en el uso de este método para su formación durante la pandemia. Conclusiones: la estrategia formativa de microlearning basada en píldoras formativas disponibles en una aplicación móvil demostró ser un elemento clave para el desarrollo de nuevas metodologías formativas digitales en el entorno hospitalario durante una situación pandémica.(AU)

Objective: to evaluate the implementation of the microlearning educational strategy through the use of a mobile application for the healthcare professionals of a university hospital during the COVID-19 pandemic. Methods: a survey was conducted on hospital staff. The visualizations of knowledge pills were monitored. The questionnaire allowed to collect information about the sociodemographic profile of participants, the use of educational mobile applications, and of the pills created ad hoc during the COVID-19 pandemic. The number of users registered in the application was of 4,572. The data obtained were analysed through descriptive analysis, using the Student’s T test and the ANOVA test for bivariate analyses. Results: the study included 633 professionals, with a mean age (SD) of 44.8 (11.1) years; 81.7% (n= 517) were female and 93.5% (n= 592) were healthcare professionals. Nurses represented 41.2% (n= 261) of the sample, and doctors 22.3% (n= 141). During the pandemic, 55.8% (n= 353) of the study subjects had worked providing direct assistance to COVID (+) patients; 94% (n= 595) visualized videos for training / getting information for their professional setting; and 94.9% reported awareness of the knowledge pills by the Formación SanidadMadrid App. The 22 knowledge pills received 25,539 visualizations in total. There was high satisfaction by participants regarding the use of this method for their training during the pandemic. Conclusions: the microlearning educational strategy, based on knowledge pills available at a mobile application, demonstrated being a key element for the development of new digital training methodologies in the hospital setting during a pandemics scenario.(AU)

Intrinsic subtypes and therapeutic decision-making in hormone receptor-positive/HER2-negative metastatic breast cancer with visceral crisis: A case report.

Background: CDK4/6 inhibitors (CDKi), namely, palbociclib, ribociclib, and abemaciclib, combined with either an aromatase inhibitor (AI) or fulvestrant are the standard first/second line for hormone receptor-positive(HR+)/HER2-negative(neg) metastatic breast cancer (MBC). However, the choice of one specific CDKi is arbitrary and based on the physician's experience with the drug, toxicity profile, and patient's preferences, whereas biomarkers for optimal patient selection have not been established so far. Moreover, upfront chemotherapy is still recommended in case of clinical presentation with visceral crisis, despite no evidence of superior benefit for chemotherapy regimens against CDKi-based regimens. Recent correlative biomarker analyses from pivotal trials of palbociclib and ribociclib showed that HR+/HER2-neg MBC might respond differently according to the molecular intrinsic subtype, with Luminal A and B tumors being sensitive to both CDKi, Basal-like being insensitive to endocrine therapy, irrespective of CDKi, and HER2-enriched tumors showing a benefit only with ribociclib-based therapy. Clinical case: We hereby present a paradigmatic clinical case of a woman affected by a relapsed HR+/HER2-neg MBC with bone and nodal lesions, presenting with a visceral crisis in the form of lymphangitis carcinomatosis and diagnosed with a molecularly HER2-enriched tumor, successfully treated with upfront ribociclib + fulvestrant. The patient experienced a complete symptomatic and radiologic remission of the lymphangitis with a partial response as best response, according to RECIST 1.1 criteria. The progression-free survival (PFS) was of 20 months, in line with the median PFS observed in the ribociclib + fulvestrant pivotal trial, where, however, patients with visceral crisis had been excluded. Conclusions: This clinical case confirms in the real-world setting that non-luminal subtypes can be found in HR+/HER2-neg disease and may have potential therapeutic implications in the metastatic setting. It also questions the recommendation of upfront chemotherapy in the case of a visceral crisis in the era of CDKi-based regimens. These issues merit further evaluation in prospective and larger studies.

Clinical and Sociodemographic Determinants of Adherence to World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Recommendations in Breast Cancer Survivors-Health-EpiGEICAM Study.

Breast cancer (BC) survivors are advised to follow the WCRF/AICR cancer prevention recommendations, given their high risk of developing a second tumour. We aimed to explore compliance with these recommendations in BC survivors and to identify potentially associated clinical and sociodemographic factors. A total of 420 BC survivors, aged 31-80, was recruited from 16 Spanish hospitals. Epidemiological, dietary and physical activity information was collected through questionnaires. A 7-item score to measure compliance with the recommendations was built according to the 2018 WCRF/AICR scoring criteria. Standardized prevalences and standardized prevalence ratios of moderate and high compliance across participant characteristics were estimated using multinomial and binary logistic regression models. The mean score was 3.9 (SD: 1.0) out of 7 points. Recommendations with the worst adherence were those of limiting consumption of red/processed meats (12% of compliance, 95% CI: 8.2-15.0) and high fibre intake (22% of compliance, 95% CI: 17.6-27.0), while the best compliance was observed for the consumption of fruits and vegetables (73% of compliance, 95% CI: 69.2-77.7). Overall, adherence was worse in women with university education and in those with first-degree relatives with BC. This information may be of interest to design and implement personalized preventive measures adapted to the characteristics of these patients.