Trastuzumab Deruxtecan With Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study.

PURPOSE: This multicenter phase Ib study investigated trastuzumab deruxtecan (T-DXd) plus nivolumab in patients with HER2-expressing metastatic breast cancer (mBC) and metastatic urothelial cancer (mUC). PATIENTS AND METHODS: Part 1 determined the recommended dose for expansion (RDE) of T-DXd plus nivolumab. Part 2 evaluated efficacy and safety; the primary endpoint was confirmed objective response rate (cORR) by independent central review. RESULTS: Seven patients with mBC were enrolled in part 1 and received T-DXd 3.2 mg/kg (4 patients) or 5.4 mg/kg (3 patients) plus nivolumab. The RDE for T-DXd was 5.4 mg/kg plus nivolumab 360 mg intravenously/3 weeks. In part 2, 32 patients with HER2-positive mBC (cohort 1; inclusive of 3 administered 5.4 mg/kg in part 1), 16 with HER2-low mBC (cohort 2), 30 with HER2-high mUC (cohort 3), and 4 with HER2-low mUC (cohort 4) were enrolled. At data cutoff (July 22, 2021), the cORR (95% CI) for cohorts 1-4 was 65.6% (46.8%-81.4%), 50.0% (24.7%-75.3%), 36.7% (19.9%-56.1%), and not assessed due to small sample size, respectively. Median treatment duration (range) with T-DXd in cohorts 1-4 was 8.9 (1-23), 6.9 (1-21), 3.9 (1-21) months, and not assessed; most common treatment-emergent adverse event was nausea (55.2%, 62.5%, 73.3%, 75.0%). Adjudicated drug-related ILD/pneumonitis rates (cohorts 1-3) were 20.7%, 0%, and 20.0% (1 grade 5 each, cohorts 1 and 3). CONCLUSION: T-DXd plus nivolumab demonstrated promising antitumor activity in HER2-expressing mBC or mUC and safety consistent with the known profile of T­DXd. ILD/pneumonitis is an important risk and requires careful monitoring and prompt intervention.

Systemic messenger RNA replacement therapy is effective in a novel clinically relevant model of acute intermittent porphyria developed in non-human primates.

OBJECTIVE: Acute intermittent porphyria (AIP) is a rare metabolic disorder caused by haploinsufficiency of hepatic porphobilinogen deaminase (PBGD), the third enzyme of the heme biosynthesis. Individuals with AIP experience neurovisceral attacks closely associated with hepatic overproduction of potentially neurotoxic heme precursors. DESIGN: We replicated AIP in non-human primates (NHPs) through selective knockdown of the hepatic PBGD gene and evaluated the safety and therapeutic efficacy of human PBGD (hPBGD) mRNA rescue. RESULTS: Intrahepatic administration of a recombinant adeno-associated viral vector containing short hairpin RNA against endogenous PBGD mRNA resulted in sustained PBGD activity inhibition in liver tissue for up to 7 months postinjection. The administration of porphyrinogenic drugs to NHPs induced hepatic heme synthesis, elevated urinary porphyrin precursors and reproduced acute attack symptoms in patients with AIP, including pain, motor disturbances and increased brain GABAergic activity. The model also recapitulated functional anomalies associated with AIP, such as reduced brain perfusion and cerebral glucose uptake, disturbances in hepatic TCA cycle, one-carbon metabolism, drug biotransformation, lipidomic profile and abnormal mitochondrial respiratory chain activity. Additionally, repeated systemic administrations of hPBGD mRNA in this AIP NHP model restored hepatic PBGD levels and activity, providing successful protection against acute attacks, metabolic changes in the liver and CNS disturbances. This approach demonstrated better efficacy than the current standards of care for AIP. CONCLUSION: This novel model significantly expands our understanding of AIP at the molecular, biochemical and clinical levels and confirms the safety and translatability of multiple systemic administration of hPBGD mRNA as a potential aetiological AIP treatment.

Clinical characterization, prognostic, and predictive values of HER2-low in patients with early breast cancer in the PALLAS trial (ABCSG-42/AFT-05/BIG-14-13/PrE0109).

BACKGROUND: Bidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC). METHODS: PALLAS is an open, international, phase 3 study evaluating the addition of palbociclib for 2 years to adjuvant ET in patients with stage II-III ER-positive/HER2-negative BC. To assess the impact of HER2 expression on patient outcomes in the phase III PALLAS trial, we analyzed (1) the association between rate of HER2-low with demographic and clinicopathological parameters, (2) the prognostic value of HER2-low status on invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS) and (3) HER2 expression's value as a predictive biomarker of response to palbociclib. HER2-low was defined as HER2 immunohistochemistry (IHC) 1 + or IHC 2 + with negative in situ hybridization (ISH). All pathologic evaluation was performed locally. Prognostic and predictive power of HER2 were assessed with Cox models. RESULTS: From the original PALLAS intention-to-treat population (N = 5753), 5304 patients (92.2%) were included in this analysis. Among these, 2254 patients (42.5%) were classified as having HER2 IHC 0 (HER2-0), and 3050 (57.5%) as having HER2-low disease (1838 with IHC 1 + and 1212 with IHC 2 +). Median follow-up was 59.8 months. HER2-low prevalence varied significantly across 21 participating countries (range 16.7% to 75.6%; p < 0.001) and was more frequent in patients enrolled in North America (63.1%) than in Europe (53.4%) or other regions (53.4%) (p < 0.001). HER2 status was not significantly associated with iDFS in a multivariable Cox model (hazard ratio 0.93, 95% confidence interval 0.81 - 1.06). No significant interaction was observed between treatment arm and HER2 status for iDFS (p = 0.43). Similar results were obtained for DRFS and OS. CONCLUSIONS: In this large, prospective, global patient cohort, no differences were observed in clinical parameters, prognosis, or differential benefit from palbociclib between HER2-0 and HER2-low tumors. Significant geographic variability was observed in the prevalence of HER2-low status, suggesting a high degree of variation in pathologic assessment of HER2 expression without impact on outcomes.

A preoperative window-of-opportunity study of oral SERD, imlunestrant, in newly diagnosed ER-positive, HER2-negative early breast cancer: Results from EMBER-2 Study.

PURPOSE: Imlunestrant is an oral SERD with favorable safety and preliminary efficacy in patients with ABC. PD biomarker data can optimize drug dosing; herein is the PD data from the EMBER-2 study. METHODS: Postmenopausal women with untreated, operable ER-positive, HER2-negative EBC were randomized to 400mg vs 800mg of imlunestrant daily for ~2 weeks before surgery. A single arm testing 200mg daily was later accrued. PD biomarker changes (ER, PR, Ki-67 by IHC, and mRNA expression of ER-related genes) were evaluated in paired tumor samples (pre-/ post-treatment). Safety and PK were also assessed. RESULTS: Among evaluable paired samples (n=75), PD profiles demonstrated consistent ER targeting between 400 and 800mg doses with less toxicity at the 400mg dose. Although inducing the lowest rate of CCCA, PD and PK results were similar for the 200mg dose. CONCLUSION: EMBER-2 combined with existing phase 1 data has identified 400mg as the optimal imlunestrant dose.

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.

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.

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.

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.

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.

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 severe acute respiratory syndrome coronavirus 2 and was generally well tolerated in a phase I trial of hospitalized patients with coronavirus disease 2019 (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 severe acute respiratory syndrome coronavirus 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. RESULTS: 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, 1.37; 95% confidence interval, .96-1.96; P = .08 for plitidepsin 1.5 mg vs control; hazard ratio, 1.06; 95% confidence interval, .73-1.53; P = .78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated. CONCLUSIONS: 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.Results from this phase III trial suggest that plitidepsin, a first-in-class antiviral, may have a positive benefit-risk ratio in the management of hospitalized patients requiring oxygen therapy for moderate COVID-19.

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.

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/.

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.

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.

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).

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.