Clinical course in older patients diagnosed with syncope treated in Spanish emergency departments: results from the Emergency Department and Elder Needs-17 study. / Evolución clínica de los pacientes mayores diagnosticados de síncope en servicios de urgencias en España: resultados del estudio EDEN-17.

OBJECTIVE: To study factors associated with hospitalization in an unselected population of patients aged 65 years or older treated for syncope in Spanish hospital emergency departments (EDs). To determine the prevalence of adverse events at 30 days in patients discharged home and the factors associated with such events. METHODS: We included all patients aged 65 years or older who were diagnosed with syncope during a single week in 52 Spanish EDs, recording patient clinical and ED case management data. We compared the findings between hospitalized patients and those discharged home, following the latter for 30 days. In discharged patients, we explored predictors of a composite adverse-event outcome (occurrence of any of the following: ED revisits, hospitalization related to the index visit, or any-cause death). RESULTS: A total of 477 patients with syncope were identified; 67 (14%) were admitted, and 5 (7.5%) died. The median (interquartile range) length of hospital stay was 6 days (3-11 days). Comorbidity increased the probability of hospitalization (odds ratio, 2.172; 95% CI, 1.013-4.655). Among the 410 patients (86%) discharged home from the ED, 9.2% experienced an adverse event within 30 days (ED revisits, 8.,1%; hospitalization, 2.2%; death, 1.5%). No factors were associated with the 30-day composite outcome. CONCLUSIONS: The majority of patients aged 65 years or older are discharged home from EDs, and 30-day adverse events, while infrequent, are difficult to predict. Hospitalization was related to comorbidity and an absence of cognitive decline.

OBJETIVO: Investigar en una muestra no seleccionada de población mayor (65 o más años) atendida en servicios de urgencias hospitalarios (SUH) españoles por síncope los factores que se asociaron con la hospitalización, prevalencia de eventos adversos (EA) a 30 días y los factores asociados a estos entre los pacientes dados de alta desde urgencias. METODO: Se incluyeron todos pacientes con 65 o más años diagnosticados de síncope durante una semana en 52 SUH españoles. Se recogieron datos de la situación clínica y el manejo en urgencias, que se compararon entre los pacientes hospitalizados y los dados de alta directamente desde urgencias. Estos últimos fueron seguidos durante 30 días y se identificaron aquellos que presentaron un EA combinado (reconsulta en urgencias u hospitalización relacionada con el evento índice y muerte por cualquier causa), y se investigaron los factores que predecían dicho EA combinado. RESULTADOS: Se identificaron 477 pacientes con síncope. Hospitalizaron 67 (14%), de los que fallecieron 5 (7,5%) y la estancia mediana fue de 6 días (RIC 3-11). La comorbilidad incrementó la probabilidad de ingreso (OR: 2,172, IC 95%: 1,013-4,655). Entre los 410 pacientes dados de alta de urgencias (86%), el 9,2% tuvo un EA durante los 30 días siguientes (reconsulta a urgencias: 8,1%; hospitalización: 2,2%; muerte: 1,5%). Ningún factor se asoció con el riesgo de EA combinado a 30 días. CONCLUSIONES: La mayoría de los pacientes con 65 años o más atendidos en los SUH por síncope son dados de alta directamente desde urgencias, y los EA a los 30 días fueron poco frecuentes, pero difíciles de predecir. La hospitalización se relacionó con presencia de comorbilidad y ausencia de deterioro cognitivo.

Nucleocytoplasmic transport senses mechanical forces independently of cell density in cell monolayers.

Cells sense and respond to mechanical forces through mechanotransduction, which regulates processes in health and disease. In single adhesive cells, mechanotransduction involves the transmission of force from the extracellular matrix to the cell nucleus, where it affects nucleocytoplasmic transport (NCT) and the subsequent nuclear localization of transcriptional regulators, such as YAP (also known as YAP1). However, if and how NCT is mechanosensitive in multicellular systems is unclear. Here, we characterize and use a fluorescent sensor of nucleocytoplasmic transport (Sencyt) and demonstrate that NCT responds to mechanical forces but not cell density in cell monolayers. Using monolayers of both epithelial and mesenchymal phenotype, we show that NCT is altered in response both to osmotic shocks and to the inhibition of cell contractility. Furthermore, NCT correlates with the degree of nuclear deformation measured through nuclear solidity, a shape parameter related to nuclear envelope tension. In contrast, YAP is sensitive to cell density, showing that the YAP response to cell-cell contacts is not via a mere mechanical effect of NCT. Our results demonstrate the generality of the mechanical regulation of NCT.

Impact of COVID-19 in the incidence of venous thromboembolism (VTE) and clinical outcomes in cancer patients: a cohort study.

PURPOSE: To determine the incidence of VTE and clinical outcomes in a cohort of cancer patients and COVID-19 infection, and to establish possible predictive factors of VTE. METHODS/PATIENTS: A single-center retrospective cohort study was performed to determine the incidence of VTE and mortality in 118 cancer patients with SARS-CoV-2 infection from March to August 2020. We calculated individual Khorana Risk and CATS-MICA scores in order to evaluate their utility to identify risk of VTE or death. Continuous variables were compared using Wilcoxon or Student's T test, and categorical variables were compared using the Chi-Square or Fisher's exact text among patients with and without VTE. A Log-Rank test was performed to detect mortality differences between the groups. RESULTS: A total of 118 patients were included. VTE global incidence was 4.2% (n = 5), and mortality 25.4% (n = 30). Obesity (p = 0.05), recent chemotherapy (p = 0.049) and use of steroids (p = 0.006) were related to higher risk of VTE in the univariate analysis, although they were not confirmed in the multivariate analysis as independent risk factors. Statistically significant differences in all-cause, COVID-19-related and cancer-related mortality according to the Khorana risk score (KRS) were observed. CATS-MICA score (CMS) also showed statistically significant differences in mortality between low- and high-risk patients. Prediction of risk of VTE development with these scores showed a tendency towards significance. CONCLUSIONS: In this cohort, VTE incidence was similar to previously reported in the general population with SARS-CoV-2 infection. KRS was associated with overall and specific-cause mortality, and might be a useful prognostic tool in this setting.

Game Dynamics in Professional Padel: Shots Per Point, Point Pace and Technical Actions.

This study aimed to determine the distributions of number of shots per point, point duration, point pace and technical actions during the match in professional men and women padel players. A total of 35,145 hits (3239 points; men = 1602 and women = 1637) were analyzed in 20 matches corresponding to quarterfinal, semifinal and final matches of the World Padel Tour 2020 season. The observations were conducted through systematic observation and involved a total of 32 players (16 men and 16 women). Men's points lasted 13.5-14.8 s, comprising 10-11 hits, resulting in a ratio of 0.80 shots per second, with no differences between sets. Women's points lasted longer than men's (14.4 to 16.2 s, p = 0.011) but included a similar number of shots per point, resulting in a lower rhythm of play (0.73-0.75 shots per second, p < 0.001), particularly in the third set (p = 0.004). Volleys, lobs and directs were used in >60% of the points, with a frequency of one to three times per point. Bandejas were used in 50-60% of the points, with a frequency of one to two times per point. Backwalls and flat smashes were used at least once in 30-48% of the points. Selective actions had a greater frequency of use in the third set (i.e., flat smash and smash x3 in women; forehand/backhand volleys and side-wall forehand in men), suggesting occasional changes in the style of play, but likely explained by the onset of fatigue. In conclusion, game volumes, intensity and actions remained broadly similar throughout professional padel matches.

A phase III randomized controlled trial of plitidepsin, a marine derived compound, in hospitalized adults with moderate COVID-19.

BACKGROUND: Plitidepsin has shown potent preclinical activity against SARS-CoV-2 and was generally well tolerated in a Phase I trial of hospitalized patients with COVID-19. NEPTUNO, a Phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients. METHODS: Included patients had documented SARS-CoV-2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety. FINDINGS: After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19-related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio [HR] 1.37, 95% confidence interval [CI] 0.96-1.96, p=0.08 for plitidepsin 1.5 mg vs control; HR 1.06, 95% CI 0.73-1.53, p=0.78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated. INTERPRETATION: Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted. FUNDING: This trial has been funded by Pharmamar, S.A. (Madrid, Spain).

Life Fatigue: A Critical Analysis.

INTRODUCTION: In recent years, euthanasia has been decriminalized or legalized in several countries. The debate on whether to legalize such a practice is open in many places and is a topic that arouses great controversy. Euthanasia has been presented as a response to situations of advanced, incurable, or irreversible disease, or situations that cause intolerable suffering to the person. However, in recent years, the claim has been asserted that this practice does not have to be associated with such situations. It may happen that a person wants to die and asks for help to do so, even if they are not in a specific clinical situation (pathology or condition) but are experiencing advanced age or present 'vital fatigue'. AIM: The objective of this article is to critically analyse the concept 'vital fatigue': define its meaning, its characteristics, its causes, and its consequences in the debate around euthanasia. To do this, a critical review of the main discussions and arguments present in the literature is made. CONCLUSIONS: It is concluded that vital fatigue can be understood as a product or manifestation of an individualistic and productivistic vision of the human being, in which its relational nature and intrinsic value remain in the background. The loss of the meaning of life also influences him. Therefore, in the face of this phenomenon, the most guaranteeing and ethical option is -we believe-accompaniment and holistic care of the person that allows the causal factors to be modulated, without the need to resort to euthanasia.

COVID-19 IgG seropositivity and its determinants in occupational groups of varying infection risks in two Andean cities of Ecuador before mass vaccination.

BACKGROUND: The COVID-19 pandemic has caused over 68.7 million infections and 1.35 million deaths in South America. There are limited data on SARS-CoV-2 seropositivity and its determinants from Andean countries prior to mass vaccinations against COVID-19. OBJECTIVE: To estimate SARS-CoV-2 seropositivity and its determinants before vaccination in occupational groups of adults presumed to have different levels of exposure and associations with potential symptomatology. METHODS: We measured seropositivity of anti-SARS-CoV-2 IgG antibodies in a cross-sectional study of vaccine-naïve adults aged 18 years and older, recruited within three occupational risk groups (defined as low [LR], moderate [MR], and high [HR]) between January and September 2021 in two Andean cities in Ecuador. Associations with risk factors were estimated using logistic regression. RESULTS: In a sample of 882 adults, IgG seropositivity for the three different occupational risk groups was 39.9% (CI 95% 35.3-44.6), 74.6% (CI 95% 66.4-81.4), and 39.0% (CI 95% 34.0-44.4) for the HR, MR, and LR groups, respectively. History of an illness with loss of taste and/or smell was significantly associated with seropositivity in all occupational groups, with adjusted ORs of 14.31 (95%CI, 5.83-35.12; p<0.001), 14.34 (95%CI 3.01-68.42; p<0.001), and 8.79 (95%CI 2.69-28.72; p<0.001), for the HR, MR, and LR groups, respectively; while fever was significant for the LR group with an adjusted OR of 1.24 (95%CI, 1.11-4.57; p = 0.025) and myalgia for the HR group with an adjusted OR of 2.07 (95%CI, 1.13-3.81; p = 0.019). CONCLUSION: Notable proportions of seropositivity were seen in all occupational groups between January and September 2021 prior to mass vaccination. Loss of taste and/or smell was strongly associated with presence of anti-SARS-CoV-2 IgG antibodies irrespective of presumed occupational exposure risk.

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.

Ego4D: Around the World in 3,000 Hours of Egocentric Video.

We introduce Ego4D, a massive-scale egocentric video dataset and benchmark suite. It offers 3,670 hours of daily-life activity video spanning hundreds of scenarios (household, outdoor, workplace, leisure, etc.) captured by 931 unique camera wearers from 74 worldwide locations and 9 different countries. The approach to collection is designed to uphold rigorous privacy and ethics standards, with consenting participants and robust de-identification procedures where relevant. Ego4D dramatically expands the volume of diverse egocentric video footage publicly available to the research community. Portions of the video are accompanied by audio, 3D meshes of the environment, eye gaze, stereo, and/or synchronized videos from multiple egocentric cameras at the same event. Furthermore, we present a host of new benchmark challenges centered around understanding the first-person visual experience in the past (querying an episodic memory), present (analyzing hand-object manipulation, audio-visual conversation, and social interactions), and future (forecasting activities). By publicly sharing this massive annotated dataset and benchmark suite, we aim to push the frontier of first-person perception. Project page: https://ego4d-data.org/.

Cardiometabolic diseases and associated risk factors in transitional rural communities in tropical coastal Ecuador.

BACKGROUND: There is a growing epidemic of chronic non-communicable diseases in low and middle-income countries, often attributed to urbanization, although there are limited data from marginalized rural populations. This study aimed to estimate prevalence of cardiometabolic diseases and associated risk factors in transitional rural communities. METHODS: A cross-sectional study of Montubio adults aged 18-94 years living in agricultural communities in a tropical coastal region of Ecuador. Data were collected by questionnaires and anthropometry, and fasting blood was analyzed for glucose, glycosylated hemoglobin, insulin, and lipid profiles. Population-weighted prevalences of diabetes, hypertension, and metabolic syndrome were estimated. Associations between potential risk factors and outcomes were estimated using multilevel regression techniques adjusted for age and sex. RESULTS: Out of 1,010 adults recruited, 931 were included in the analysis. Weighted prevalences were estimated for diabetes (20.4%, 95% CI 18.3-22.5%), hypertension (35.6%, 95% CI 29.0-42.1%), and metabolic syndrome (54.2%. 95% CI 47.0-61.5%) with higher prevalence observed in women. Hypertension prevalence increased with age while diabetes and metabolic syndrome peaked in the 6th and 7th decades of life, declining thereafter. Adiposity indicators were associated with diabetes, hypertension, and metabolic syndrome. CONCLUSION: We observed an unexpectedly high prevalence of diabetes, hypertension, and metabolic syndrome in these marginalized agricultural communities. Transitional rural communities are increasingly vulnerable to the development of cardiometabolic risk factors and diseases. There is a need for targeted primary health strategies to reduce the burden of premature disability and death in these communities.

Creation of an Isogenic Human iPSC-Based RGC Model of Dominant Optic Atrophy Harboring the Pathogenic Variant c.1861C>T (p.Gln621Ter) in the OPA1 Gene.

Autosomal dominant optic atrophy (ADOA) is a rare progressive disease mainly caused by mutations in OPA1, a nuclear gene encoding for a mitochondrial protein that plays an essential role in mitochondrial dynamics, cell survival, oxidative phosphorylation, and mtDNA maintenance. ADOA is characterized by the degeneration of retinal ganglion cells (RGCs). This causes visual loss, which can lead to legal blindness in many cases. Nowadays, there is no effective treatment for ADOA. In this article, we have established an isogenic human RGC model for ADOA using iPSC technology and the genome editing tool CRISPR/Cas9 from a previously generated iPSC line of an ADOA plus patient harboring the pathogenic variant NM_015560.3: c.1861C>T (p.Gln621Ter) in heterozygosis in OPA1. To this end, a protocol based on supplementing the iPSC culture media with several small molecules and defined factors trying to mimic embryonic development has been employed. Subsequently, the created model was validated, confirming the presence of a defect of intergenomic communication, impaired mitochondrial respiration, and an increase in apoptosis and ROS generation. Finally, we propose the analysis of OPA1 expression by qPCR as an easy read-out method to carry out future drug screening studies using the created RGC model. In summary, this model provides a useful platform for further investigation of the underlying pathophysiological mechanisms of ADOA plus and for testing compounds with potential pharmacological action.

Abemaciclib plus endocrine therapy for HR+, HER2-, node-positive, high-risk early breast cancer: a plain language summary of the monarchE study.

WHAT IS THIS SUMMARY ABOUT?: This article summarizes the most recent results of the monarchE study. This study was completed in participants with a type of breast cancer called HR+, HER2-, node-positive, high-risk early breast cancer. In this study, abemaciclib, a non-chemotherapy treatment, was administered with standard of care endocrine therapy after curative surgery. Most participants had received prior chemotherapy and/or radiotherapy. The study investigated if abemaciclib helped participants live longer without their cancer returning compared with participants who only received standard of care endocrine therapy. The study participants were assigned to 1 of 2 treatment groups. Participants in Group A were assigned to receive standard of care endocrine therapy with abemaciclib for 2 years, followed by endocrine therapy for a total of at least 5 years. Participants in Group B were assigned to receive standard of care endocrine therapy only for at least 5 years. The effect of treatment was compared between these 2 groups. WHAT WERE THE RESULTS?: Overall, the results showed that the cancer was 34% less likely to come back after surgery in the participants in Group A (abemaciclib plus endocrine therapy) compared with those in Group B (endocrine therapy only). At 4 years since the start of the study treatment, more participants who received the combination of abemaciclib plus endocrine therapy remained free of cancer compared with participants who received endocrine therapy alone (86% versus 79%). Participants who received abemaciclib plus endocrine therapy had more side effects than those who received endocrine therapy alone, but most of these effects were mild to moderate and reversible upon the end of therapy. The most common side effects in the abemaciclib group were diarrhea, infections, low number of white blood cells, and tiredness. WHAT DO THE RESULTS MEAN?: This study found that administering abemaciclib in combination with standard endocrine therapy after curative breast surgery helped lower the risk of cancer returning in people with HR+, HER2-, node-positive, high-risk early breast cancer. Abemaciclib is a new treatment option for people with this diagnosis. People with high-risk early breast cancer should always talk to their doctors and nurses before making any decisions about their treatment.Clinical Trial Registration: NCT03155997 (monarchE study).

Store-and-forward teledermatology in a Spanish health area significantly increases access to dermatology expertise.

INTRODUCTION: Teledermatology is the practice of dermatology through communication technologies. The aim of this study is to analyze its implementation in a Spanish health area during its first two years. METHODS: Cross-sectional descriptive study. It included interconsultations between dermatologists and family physicians in the Salamanca Health Area (Spain) after the implementation of the non-face-to-face modality over a period of two consecutive years. A total of 25,424 consultations were performed (20,912 face-to-face and 4,512 non-face-to-face); 1000 were selected by random sampling, half of each modality. MAIN MEASURES: referral rate, response time and resolution time, type of pathology, diagnostic concordance, and quality of consultation. RESULTS: The annual referral rate was 42.9/1000 inhabitants (35.3 face-to-face and 7.6 non-face- to-face). The rate of face-to-face referrals was higher in urban areas (37.1) and the rate of non- face-to-face referrals in rural areas (10.4). The response time for non-face-to-face consultations was 2.4 ± 12.7 days and 56 ± 34.8 days for face-to-face consultations (p < 0.001). The resolution rate for non-face-to-face consultations was 44%. Diagnostic concordance, assessed by the kappa index, was 0.527 for face-to-face consultations and 0.564 for non-face-to-face consultations. Greater compliance with the quality criteria in the non-attendance consultations. CONCLUSIONS: Teledermatology appears to be an efficient tool in the resolution of dermatological problems, with a rapid, effective, and higher quality response for attention to skin pathologies. REGISTRY: ClinicalTrials.gov Identifier: NCT05625295. Registered on 21 November 2022 ( https://clinicaltrials.gov/ct2/show/ NCT05625295).

BODYFAT: a new calculator to determine the risk of being overweight validated in Spanish children between 11 and 17 years of age.

The assessment of body fat of children in primary care requires consideration of the dynamic changes in height, weight, lean mass, and fat mass during childhood growth. To achieve this, we aim to develop a predictive equation based on anthropometric values, with optimal diagnostic utility. This is a cross-sectional observational study, involving schoolgoers aged 11-17 years in the Vigo metropolitan area. Out of 10,747 individuals, 577 were randomly recruited. VARIABLES: age, sex, ethnicity/country of origin, weight, height, 8 skinfolds, 3 diameters, 7 perimeters, and 85% percentile of body fat mass as the gold standard. Generalized additive regression was selected by cross-validation and compared using receiver operating characteristic curves (ROC curves). Sensitivity, specificity, positive and negative predictive values, true positive and true negative values, false positive and false negative values, accuracy, and positive and negative likelihood ratios were calculated. Two models were identified. The optimal model includes sex, weight, height, leg perimeter, and arm perimeter, with sensitivity of 0.93 (0.83-1.00), specificity of 0.91 (0.83-0.96), accuracy of 0.91 (0.84-0.96), and area under the curve (AUC) of 0.957 (0.928-0.986). The second model includes sex, age, and body mass index, with sensitivity of 0.93 (0.81-1.00), specificity of 0.90 (0.80-0.97), accuracy of 0.90 (0.82-0.96), and an AUC of 0.944 (0.903-0.984). CONCLUSION: Two predictive models, with the 85th percentile of fat mass as the gold standard, built with basic anthropometric measures, show very high diagnostic utility parameters. Their calculation is facilitated by a complementary online calculator. WHAT IS KNOWN: • In routine clinical practice, mainly in primary care, BMI is used to determine overweight and obesity. This index has its weaknesses in the assessment of children. WHAT IS NEW: • We provide a calculator whose validated algorithm, through the determination of fat mass by impedanciometry, makes it possible to determine the risk of overweight and obesity in the community setting, through anthropometric measurements, providing a new practical, accessible and reliable model that improves the classification of overweight and obesity in children with respect to that obtained by determining BMI.

"Positioning of tucatinib in the new clinical scenario of HER2-positive metastatic breast cancer: An Italian and Spanish consensus paper".

INTRODUCTION: Advancements in monoclonal antibodies, tyrosine kinase inhibitors, and antibody drug conjugates (ADCs) have notably enhanced outcomes for metastatic HER2-positive breast cancer patients. Despite the expanding treatment options and clinical complexities, determining the optimal sequence of HER2-targeted therapies remains partly uncertain, influenced by various factors. METHODS: To refine HER2-positive metastatic breast cancer management, particularly regarding tucatinib's position, a Steering Committee of leading oncologists in breast cancer care devised a panel of statements via a Delphi approach, focusing on five key topics: general clinical management, therapeutic approaches for patients with HER2-positive breast cancer and brain metastases, treatment sequence, and tucatinib's safety and efficacy. RESULTS: A total of 29 statements were deliberated, with strong consensus achieved for most. However, no consensus emerged regarding the management of brain progression alongside stable extracranial disease: 48 % advocated for switching to tucatinib, while 53 % favored a stereotactic brain radiotherapy (SBRT) approach if feasible. CONCLUSION: The unanimous consensus attained in this Delphi panel, particularly regarding tucatinib's efficacy and safety, underscores oncologists' recognition of its clinical significance based on existing trial data. These findings align closely with current literature, shedding light on areas necessitating further investigation, not thoroughly explored in prior studies. Moreover, the results underscore the scarcity of data on managing brain progression alongside stable extracranial disease, emphasizing the imperative for dedicated research to address these gaps and yield definitive insights.

Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2- advanced breast cancer: a real-world evidence cohort.

PURPOSE: Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. METHODS: A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates. RESULTS: One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15 months (interquartile range: 1-56 months). The median age at diagnosis was 49 years (range: 35-90 years). The estimated mPFS was 6.0 months (95%CI 5.3-7.8 months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18 months (8.7 months, 95%CI 6.6-11.3 months), in patients w/o visceral metastases (8.0 months, 95%CI 5.8-10.5 months), and chemotherapy-naïve in the metastatic setting (7.2 months, 95%CI 5.9-8.4 months). CONCLUSION: This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.