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Abstract Phosphate is essential in living organisms and its blood levels are regulated by a complex network involving the kidneys, intestine, parathyroid glands, and the skeleton. The crosstalk between these organs is executed primarily by three hormones, calcitriol, parathyroid hormone, and fibroblast growth factor 23. Largely due to a higher intake of ultraprocessed foods, dietary phosphate intake has increased in the last decades. The average intake is now about twice the recommended dietary allowance. Studies investigating the side effect of chronic high dietary phosphate intake suffer from incomplete dietary phosphate assessment and, therefore, often make data interpretation difficult. Renal excretion is quickly adapted to acute and chronic phosphate intake. However, at the high ends of dietary intake, renal adaptation, even in pre-existing normal kidney function, apparently is not perfect. Experimental intervention studies suggest that chronic excess of dietary phosphate can result in sustained higher blood phosphate leading to hyperphosphatemia. Evidence exists that the price of the homeostatic response (phosphaturia in response to phosphate loading/hyperphosphatemia) is an increased risk for declining kidney function, partly due by intraluminal/tubular calcium phosphate particles that provoke renal inflammation. High dietary phosphate intake and hyperphosphatemia are progression factors for declining kidney function and are associated with higher cardiovascular disease and mortality risk. This is best established for pre-existing chronic kidney disease, but epidemiological and experimental data strongly suggest that this holds true for subjects with normal renal function as well. Here, we review the latest advances in phosphate intake and kidney function decline.

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).

The MINDACT trial showed excellent 5-year distant metastasis-free survival of 94·7% (95% CI 92·5–96·2) in patients with breast cancer of high clinical and low genomic risk who did not receive chemotherapy. We present long-term follow-up results together with an exploratory analysis by age. MINDACT was a multicentre, randomised, phase 3 trial done in 112 academic and community hospitals in nine European countries. Patients aged 18–70 years, with histologically confirmed primary invasive breast cancer (stage T1, T2, or operable T3) with up to three positive lymph nodes, no distant metastases, and a WHO performance status of 0–1 were enrolled and their genomic risk (using the MammaPrint 70-gene signature) and clinical risk (using a modified version of Adjuvant! Online) were determined. Patients with low clinical and low genomic risk results did not receive chemotherapy, and patients with high clinical and high genomic risk did receive chemotherapy (mostly anthracycline-based or taxane-based, or a combination thereof). Patients with discordant risk results (ie, patients with high clinical risk but low genomic risk, and those with low clinical risk but high genomic risk) were randomly assigned (1:1) to receive chemotherapy or not based on either the clinical risk or the genomic risk. Randomisation was done centrally and used a minimisation technique that was stratified by institution, risk group, and clinical–pathological characteristics. Treatment allocation was not masked. The primary endpoint was to test whether the distant metastasis-free survival rate at 5 years in patients with high clinical risk and low genomic risk not receiving chemotherapy had a lower boundary of the 95% CI above the predefined non-inferiority boundary of 92%. In the primary test population of patients with high clinical risk and low genomic risk who adhered to the treatment allocation of no chemotherapy and had no change in risk post-enrolment. Here, we present updated follow-up as well as an exploratory analysis of a potential age effect (≤50 years vs >50 years) and an analysis by nodal status for patients with hormone receptor-positive and HER2-negative disease. These analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00433589, and the European Clinical Trials database, EudraCT2005–002625–31. Recruitment is complete and further long-term follow-up is ongoing. Between Feb 8, 2007, and July 11, 2011, 6693 patients were enrolled. On Feb 26, 2020, median follow-up was 8·7 years (IQR 7·8–9·7). The updated 5-year distant metastasis-free survival rate for patients with high clinical risk and low genomic risk receiving no chemotherapy (primary test population, n=644) was 95·1% (95% CI 93·1–96·6), which is above the predefined non-inferiority boundary of 92%, supporting the previous analysis and proving MINDACT as a positive de-escalation trial. Patients with high clinical risk and low genomic risk were randomly assigned to receive chemotherapy (n=749) or not (n=748); this was the intention-to-treat population. The 8-year estimates for distant metastasis-free survival in the intention-to-treat population were 92·0% (95% CI 89·6–93·8) for chemotherapy versus 89·4% (86·8–91·5) for no chemotherapy (hazard ratio 0·66; 95% CI 0·48–0·92). An exploratory analysis confined to the subset of patients with hormone receptor-positive, HER2-negative disease (1358 [90.7%] of 1497 randomly assigned patients, of whom 676 received chemotherapy and 682 did not) shows different effects of chemotherapy administration on 8-year distant metastasis-free survival according to age: 93·6% (95% CI 89·3–96·3) with chemotherapy versus 88·6% (83·5–92·3) without chemotherapy in 464 women aged 50 years or younger (absolute difference 5·0 percentage points [SE 2·8, 95% CI −0·5 to 10·4]) and 90·2% (86·8–92·7) versus 90·0% (86·6–92·6) in 894 women older than 50 years (absolute difference 0·2 percentage points [2·1, −4·0 to 4·4]). The 8-year distant metastasis-free survival in the exploratory analysis by nodal status in these patients was 91·7% (95% CI 88·1–94·3) with chemotherapy and 89·2% (85·2–92·2) without chemotherapy in 699 node-negative patients (absolute difference 2·5 percentage points [SE 2·3, 95% CI −2·1 to 7·2]) and 91·2% (87·2–94·0) versus 89·9% (85·8–92·8) for 658 patients with one to three positive nodes (absolute difference 1·3 percentage points [2·4, −3·5 to 6·1]). With a more mature follow-up approaching 9 years, the 70-gene signature shows an intact ability of identifying among women with high clinical risk, a subgroup, namely patients with a low genomic risk, with an excellent distant metastasis-free survival when treated with endocrine therapy alone. For these women the magnitude of the benefit from adding chemotherapy to endocrine therapy remains small (2·6 percentage points) and is not enhanced by nodal positivity. However, in an underpowered exploratory analysis this benefit appears to be age-dependent, as it is only seen in women younger than 50 years where it reaches a clinically relevant threshold of 5 percentage points. Although, possibly due to chemotherapy-induced ovarian function suppression, it should be part of informed, shared decision making. Further study is needed in younger women, who might need reinforced endocrine therapy to forego chemotherapy. European Commission Sixth Framework Programme.

SummaryPrimary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.

Key Points A range of alternative techniques to wire-guided localization are available for localization of neoplastic lesions prior to surgical management of nonpalpable breast cancer The use of radioguided localization is supported by data from meta-analyses; however, overall utilization of this technique has been poor owing to the logistical and legislative issues associated with radioisotope use More than 95% of localization procedures include ultrasonography, making intraoperative ultrasonography a logical alternative, but this method requires evidence from randomized controlled trials and implementation of training programmes for surgeons Techniques that use the principles of radioguided localization, but that are radioisotope free, could form the basis of future therapeutic options and warrant investigation in adequately powered clinical trials Non-invasive surgery using high-intensity focused ultrasound is in its infancy, but could potentially enable real-time visualization and therapy of lesions as an outpatient procedure Currently, more than a third of all breast cancers are nonpalpable at diagnosis, and this proportion is expected to increase owing to the expansion of effective breast-screening programmes. Surgical excision combined with axillary staging is the standard of care for patients with nonpalpable breast cancers, and requires accurate localization of the primary tumour prior to resection. This Review provides an overview of the various techniques available for the localization and surgical management of nonpalpable breast cancer, their advantages and disadvantages, and future directions for the development of new technologies. Breast cancer is the most-common cancer among women worldwide, and over one-third of all cases diagnosed annually are nonpalpable at diagnosis. The increasingly widespread implementation of breast-screening programmes, combined with the use of advanced imaging modalities, such as magnetic resonance imaging (MRI), will further increase the numbers of patients diagnosed with this disease. The current standard management for nonpalpable breast cancer is localized surgical excision combined with axillary staging, using sentinel-lymph-node biopsy in the clinically and radiologically normal axilla. Wire-guided localization (WGL) during mammography is a method that was developed over 40 years ago to enable lesion localization preoperatively; this technique became the standard of care in the absence of a better alternative. Over the past 20 years, however, other technologies have been developed as alternatives to WGL in order to overcome the technical and outcome-related limitations of this technique. This Review discusses the techniques available for the surgical management of nonpalpable breast cancer; we describe their advantages and disadvantages, and highlight future directions for the development of new technologies.

Background: The aging population is increasing rapidly, much faster than our understanding on how to promote healthy aging free of multimorbidities. The aging kidney shows a decline in its function. Whether this decline is preventable or physiological is still debated. Main risks factors for developing CKD are aging common comorbidites, such as hypertension, diabetes, and obesity. Phosphate is vital for our organism, but it is also present in a great variety of food products as food additive and preservative. Due to the higher consumption of processed food in the last century, concern has arisen if a chronic high consumption of phosphate may be toxic impacting on healthy aging. Summary: Several studies show an association between higher serum phosphate levels and a higher risk of overall mortality and cardiovascular disease. Moreover, higher phosphate levels also worsen CKD progression and may contribute to renal dysfunction in healthy individuals. Acute high phosphate intake is rare but can cause acute kidney injury. Yet, the question if controlling phosphate intake may modulate serum phosphate concentrations remains unanswered, as assessment of phosphate intake is still a difficult task. Phosphate consumption estimations by dietary recalls are largely underestimated, especially in populations groups consuming high amount of processed food. Key Message: A healthy diet with phosphate source from food may contribute to promote healthy aging and longevity.

There is much literature about the role of 2-[ F]FDG PET/CT in patients with breast cancer (BC). However, there exists no international guideline with involvement of the nuclear medicine societies about this subject. To provide an organized, international, state-of-the-art, and multidisciplinary guideline, led by experts of two nuclear medicine societies (EANM and SNMMI) and representation of important societies in the field of BC (ACR, ESSO, ESTRO, EUSOBI/ESR, and EUSOMA). Literature review and expert discussion were performed with the aim of collecting updated information regarding the role of 2-[ F]FDG PET/CT in patients with no special type (NST) BC and summarizing its indications according to scientific evidence. Recommendations were scored according to the National Institute for Health and Care Excellence (NICE) criteria. Quantitative PET features (SUV, MTV, TLG) are valuable prognostic parameters. In baseline staging, 2-[ F]FDG PET/CT plays a role from stage IIB through stage IV. When assessing response to therapy, 2-[ F]FDG PET/CT should be performed on certified scanners, and reported either according to PERCIST, EORTC PET, or EANM immunotherapy response criteria, as appropriate. 2-[ F]FDG PET/CT may be useful to assess early metabolic response, particularly in non-metastatic triple-negative and HER2+ tumours. 2-[ F]FDG PET/CT is useful to detect the site and extent of recurrence when conventional imaging methods are equivocal and when there is clinical and/or laboratorial suspicion of relapse. Recent developments are promising. 2-[ F]FDG PET/CT is extremely useful in BC management, as supported by extensive evidence of its utility compared to other imaging modalities in several clinical scenarios.

Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.

Nowadays, emotional intelligence is not only understood as the recognition of our own emotions but also the regulation of these emotions. In the field of sports, the concept of sports leadership is increasingly relevant, understood as a behavioral and cognitive process closely related to sports success, based on interpersonal relationships, trust, respect and the feeling of coherence. In this study, we intend to analyze the relationship between sports success and emotional intelligence to verify their relationship and the influence of other variables such as sports anxiety. As a sample, we took a total of 165 active sportsmen and women studying for both undergraduate and master’s degrees related to the sciences of physical activity and sport. The expected results aim to demonstrate the relationship between emotional intelligence, sports leadership and sports anxiety.